Metagenomi Inc

Previous wording

We are a precision genetic medicines company committed to developing curative therapeutics for patients using our proprietary, comprehensive metagenomics-derived genome editing toolbox. Genetic diseases are caused by a diverse set of mutations that have been largely inaccessible by genome engineering approaches to date. Genetic mutations are seen in a variety of forms, including deletions, insertions, single-base-pair changes and sequence repeats, and are found throughout the genome and across a variety of different cell types, tissues, and organ systems. Additionally, many diseases lack a genetic origin but have the potential to be effectively and permanently addressed through genome editing. We are harnessing the power of metagenomics, the study of genetic material recovered from the natural environment, to unlock four billion years of microbial evolution to discover and develop a suite of novel editing tools capable of correcting any type of genetic mutation found anywhere in the genome. Our platform combines AI, including machine learning, and proprietary algorithms run on expansive cloud computing infrastructure to screen for novel clustered regularly interspaced short palindromic repeat (“CRISPR”) nucleases and other effector enzymes at high speed.

Current wording

We are a precision genetic medicines company committed to developing curative therapeutics for patients using our proprietary, comprehensive metagenomics-derived genome editing toolbox. We are harnessing the power of metagenomics, the study of genetic material recovered from the natural environment, to unlock four billion years of microbial evolution to discover and develop a suite of novel editing tools capable of correcting any type of genetic mutation found anywhere in the genome. Our platform combines AI and proprietary algorithms run on expansive cloud computing infrastructure to screen for novel clustered regularly interspaced short palindromic repeat (“CRISPR”) nucleases and other effector enzymes at high speed.

Previous wording

Our comprehensive genome editing toolbox includes programmable nucleases, base editors, RNA-mediated integration systems (“RIGS”), including prime editing systems and our larger RIGS systems, and DNA-clustered CRISPR-associated transposases (“CASTs”). All components of our toolbox have been discovered and derived from our proprietary metagenomics library. We have assembled a full suite of differentiated tools that, together, can potentially effectuate any desired gene modification – gene knock-down, gene knock-in and replacements. All elements of our toolbox are wholly owned, and we have constructed a broad patent estate that protects our intellectual property. We anticipate that our toolbox will continue to expand as we discover, interrogate, and optimize our novel editing systems.

Current wording

Our comprehensive genome editing toolbox includes programmable nucleases, base editors, RNA-mediated integration systems (“RIGS”) for small corrections (“prime editing”) as well as for larger integrations, and CRISPR-associated transposases (“CASTs”) for doing large integrations with DNA. These tools form a toolbox that can potentially make any desired gene modification – gene knock-down, gene knock-in as well as small and large genetic changes. In addition to overcoming the activity, targetability, and specificity limitations of first-generation systems, our toolbox includes ultra small editing systems, designed to have broad compatibility with viral and nonviral delivery technologies, to address the full spectrum of genetic medicine for hepatic- and extrahepatic therapeutic indications. All elements of our toolbox are wholly owned, and we have constructed a broad patent estate that protects our intellectual property. We anticipate that our toolbox will continue to expand as we discover, interrogate, and optimize our novel editing systems.

Previous wording

We are taking a stepwise approach deploying our genome editing toolbox to develop potentially curative therapies for patients. Our lead programs are selected to both address important diseases and to establish new standards in targetability, precision, efficiency, and scope of editing capabilities. Each of these indications was chosen based on our conviction in the underlying disease biology, existence of validating preclinical and clinical data, availability of pharmacodynamic and translational tools to assess early proof-of-concept, relevant value supporting outcome measures, and ongoing clinical unmet need. While we do not currently have any approved products and all of our product candidates are preclinical, our lead programs capture an ever-growing set of translational learnings and insights that will inform and accelerate future therapeutic programs. Ultimately, we intend to prosecute a genetic medicine therapeutic development strategy across a broad array of diseases and target organs including liver, central nervous system, muscle, kidney, and lung.

Current wording

We are taking a stepwise approach deploying our genome editing toolbox to develop potentially curative therapies for patients. Our lead programs are selected to both address important diseases and to establish new standards in targetability, precision, efficiency, and scope of editing capabilities. Each of these indications was chosen based on our conviction in the underlying disease biology, existence of validating preclinical and clinical data, availability of pharmacodynamic and translational tools to assess early proof-of-concept, relevant value supporting outcome measures, and ongoing clinical unmet need. While we do not currently have any approved products and all of our product candidates are preclinical, our lead programs capture an ever-growing set of translational learnings and insights that will inform and potentially accelerate future therapeutic programs. Ultimately, we intend to prosecute a genetic medicine therapeutic development strategy across a broad array of diseases and target organs including liver, central nervous system, muscle, kidney, and lung.

Previous wording

Our program is designed to insert a Factor VIII (“FVIII”) DNA cassette into a “safe harbor location,” within an intron of the albumin gene that is not expected to have deleterious effects. FVIII expression is then driven off the strength of the native albumin promoter. Our lead Hemophilia A genome editing strategy has two components. First, a lipid nanoparticle (“LNP”) is designed to deliver mRNA along with a gRNA to the liver in order to produce a highly efficient and specific nuclease that creates a precise cut at the albumin safe harbor gene locus. Next, an adeno-associated virus (“AAV”) vector that is designed to deliver the donor template FVIII DNA that becomes inserted into the nuclease cut site by a naturally occurring DNA repair process called non-homologous end joining.

Current wording

Our program is designed to insert a Factor VIII (“FVIII”) DNA cassette into a “safe harbor location,” within an intron of the albumin gene that is not expected to have deleterious effects. FVIII expression is then driven off the strength of the native albumin promoter. Our lead hemophilia A genome editing strategy has two components. A lipid nanoparticle (“LNP”) is designed to deliver mRNA along with a gRNA to the liver in order to produce a highly efficient and specific nuclease that creates a precise cut at the albumin safe harbor gene locus. Additionally, an adeno-associated virus (“AAV”) vector that is designed to deliver the donor template FVIII DNA that becomes inserted into the nuclease cut site by a naturally occurring DNA repair process called non-homologous end joining.

Previous wording

In an ongoing NHP study, we demonstrated integration of a surrogate cynomolgus-FVIII cassette (used to avoid immune response that would occur with a foreign human FVIII protein) and observed therapeutically relevant levels of the cyno-FVIII protein in all 3 treated animals that was extended for 4.5 months. We recently presented this data in a late breaking session at the World Federation of Hemophilia World Congress, in April 2024. We anticipate nominating a development candidate for this program in mid-year 2024, and we plan to present 12-month durability data for FVIII expression in this ongoing NHP study in the second half of 2024. In parallel, we are manufacturing mRNA, gRNA, AAV and LNP to support future investigational new drug (“IND”) enabling studies.

Current wording

In an ongoing non-human primate (“NHP”) study, we demonstrated integration of a surrogate cynomolgus-FVIII cassette (used to avoid immune response that would occur with a foreign human FVIII protein) and observed therapeutically relevant levels of the cyno-FVIII protein in all 3 treated animals that was extended for 4.5 months. We presented this data in a late breaking session at the World Federation of Hemophilia World Congress, in April 2024.

Previous wording

Our development program in Transthyretin amyloidosis (“TTR”) aims to provide efficient TTR knockdown and halt further deposition of amyloid fibrils. Along with our partner Ionis Pharmaceuticals, Inc. (“Ionis”), we are currently in advanced stages of nuclease and guide selection, having achieved more than 90% knock-down of human TTR protein in a humanized TTR mouse model, and expect to move into NHP studies in 2024.

Current wording

Transthyretin amyloidosis is a disease of misfolded and aggregated transthyretin (“TTR”) protein that can deposit in tissues causing organ dysfunction, primarily in the heart and/or peripheral nerves. Our development program in TTR aims to provide efficient TTR knockdown and halt further deposition of amyloid fibrils. Along with our partner Ionis, we have achieved more than 90% knock-down of human TTR protein in a humanized TTR mouse model, and have initiated NHP studies.

Previous wording

Our Cardiovascular program is designed to knock-down the expression of angiotensinogen (“AGT”) in the liver using one of our programmable nucleases to generate a durable reduction in blood pressure from a single treatment. Along with our partner Ionis we are currently in advanced stages of nuclease and guide screening, having achieved 85% - 93% knock-down of human AGT protein in a humanized AGT mouse model, and expect to move into NHP studies in late 2024 or early 2025.

Current wording

The refractory hypertension program is designed to knock-down the expression of AGT in the liver using one of our programmable nucleases to generate a durable reduction in blood pressure from a single treatment. Along with our partner Ionis, we have achieved greater than 85% knock-down of human AGT protein in a humanized AGT mouse model, and have plans to initiate NHP studies.

Previous wording

To date, we have identified thousands of novel CRISPR type II, type V and highly efficient ultra-small (“SMART”) nucleases, expanding the collection of known programmable nucleases by mining our proprietary metagenomics database. This allows us to potentially select the ideal nuclease for targeting any given gene in a site-specific manner, overcoming a major limitation of first-generation CRISPR/Cas9 systems.

Current wording

To date, we have identified thousands of novel CRISPR type II, type V and highly efficient ultra-small (SMall Arginine-Rich sysTems or SMART) nucleases, expanding the collection of known programmable nucleases by mining our proprietary metagenomics database. This allows us to potentially select the ideal nuclease for targeting any given gene in a site-specific manner, overcoming a major limitation of first-generation CRISPR/Cas9 systems.

Previous wording

The chassis of our nucleases can be leveraged by adding on additional effector enzymes to create base editors capable of single nucleotide changes in the genome. We showed that by using PAM interacting domain engineering, we expanded the genome targetability of our base editors by 5-fold compared to SpCas9 base editors. Additionally, we demonstrated our ability to engineer our SMART nucleases into SMART base editors. We believe our SMART base editors, which are as small as 623 amino acids, represent some of the smallest base editing systems in the industry. As the size of these systems are well-within the packaging limits of AAV vectors, our SMART base editors could greatly expand the potential to leverage AAV delivery across a variety of indications.

Current wording

The chassis of our nucleases can be leveraged by adding on additional effector enzymes to create base editors capable of single nucleotide changes in the genome. We showed that by using PAM interacting domain engineering, we expanded the genome targetability of our base editors by 5-fold compared to SpCas9 base editors. We recently achieved multiplex base editing proof-of-concept and plan to present this data at a scientific conference in the second half of 2024.

Previous wording

Our big RIGS are being developed for the programmable integration of large transgenes delivered as RNA, with the potential to address any genetic disease requiring a large gene integration. Using proprietary Reverse Transcriptases we demonstrated what we believe to be the first-ever targeted integration of >900 bp in human cells with our big RIGS using all-RNA delivery. We consider this to be a major step forward in the gene editing space, as these systems could be delivered entirely as RNA, compatible with current LNP delivery technologies, and could enable large, targeted exogenous gene integrations.

Current wording

We recently achievedin vitro proof-of-concept using our RIGS for a small gene correction in undisclosed liver targets. Additionally, using proprietary reverse transcriptases we demonstrated what we believe to be the first-ever targeted integration of >900 bp in human cells with our RIGS using all-RNA delivery. We consider this to be a major step forward in the gene editing space, as these systems could be delivered entirely as RNA, compatible with current LNP delivery technologies, and could enable large, targeted exogenous gene integrations.

Previous wording

CASTs are naturally occurring programmable transposase systems with the ability to site-specifically integrate large transgenes delivered as DNA, and with the potential to address any genetic disease requiring a large gene integration. Our CASTs are being developed in order to enable large, >10,000 base pairs, targeted genomic integrations for therapeutic applications. We recently demonstrated initial preclinical proof-of-capability for our CASTs with a targeted integration of a large DNA template in the genome of mammalian cells.

Current wording

CASTs are naturally occurring programmable transposase systems with the ability to site-specifically integrate large transgenes delivered as DNA, and with the potential to address any genetic disease requiring a large gene integration. Our CASTs are being developed in order to enable large, >10,000 base pairs, targeted genomic integrations for therapeutic applications. We recently achievedin vitro proof-of-concept for large gene integration using our potentially industry leading, compact CAST technology, with publication pending.

Previous wording

On April 26, 2024 (the “Termination Date”), we and ModernaTx, Inc. (“Moderna”) mutually terminated the Strategic Collaboration and License Agreement, dated October 29, 2021 (the “Moderna Agreement”), by and between us and Moderna. The Moderna Agreement was terminated pursuant to a Mutual Termination Agreement (the “Termination Agreement”), dated as of April 26, 2024, by and between us and Moderna. Pursuant to the Termination Agreement, we regained full development and commercialization rights to our wholly-owned base editing and RIGS that were subject to the Moderna Agreement. Effective as of the Termination Date, the Moderna Agreement was terminated in its entirety and the rights and licenses granted by us to Moderna terminated in all respects. Following the Termination Date, we will not be entitled to receive any future payments from Moderna pursuant to the Termination Agreement or Moderna Agreement.

Current wording

On April 26, 2024 (the “Termination Date”), we and ModernaTx, Inc. (“Moderna”) mutually terminated the Strategic Collaboration and License Agreement, dated October 29, 2021 (the “Moderna Agreement”), by and between us and Moderna. The Moderna Agreement was terminated pursuant to a Mutual Termination Agreement (the “Termination Agreement”), dated as of April 26, 2024, by and between us and Moderna. Pursuant to the Termination Agreement, we regained full development and commercialization rights to our wholly-owned base editing and RIGS technologies that were subject to the Moderna Agreement. Effective as of the Termination Date, the Moderna Agreement was terminated in its entirety and the rights and licenses granted by us to Moderna terminated in all respects. We are not entitled to receive any future payments from Moderna pursuant to the Termination Agreement or Moderna Agreement.

Previous wording

As part of our strategy, we have entered into collaborations with third parties for one or more of our programs or product candidates we may develop. For example, in June 2022, we entered into a Development, Option and License Agreement with Affini-T Therapeutics, Inc. (“Affini-T”) (the “Affini-T Agreement”) to develop and commercialize gene edited T-cell receptor (“TCR”)-based therapeutic products exclusively in the field of treatment, prevention or diagnosis of any human cancer using products with any engineered primary TCR alpha/beta T cells and non-exclusively in the field of treatment, prevention or diagnosis of any human cancer using products with certain other engineered immune cells worldwide, and in November 2022, we entered into a Collaboration and License Agreement with Ionis to research, develop and commercialize investigational medicines using genome editing technologies. In October 2021, we entered into the Moderna Agreement with Moderna, focused on advancing new genome editing system for in vivo human therapeutic applications, and in April 2024, we and Moderna mutually terminated the Moderna Agreement. Refer to Note 7 in our condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for additional information related to the terms of the agreements between us and our collaborators and Note 12 in our condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for additional information related to the termination of the Moderna Agreement.

Current wording

As part of our strategy, we have entered into collaborations with third parties for one or more of our programs or product candidates we may develop. For example, in June 2022, we entered into a Development, Option and License Agreement with Affini-T Therapeutics, Inc. (“Affini-T”) (the “Affini-T Agreement”) to develop and commercialize gene edited T-cell receptor (“TCR”)-based therapeutic products exclusively in the field of treatment, prevention or diagnosis of any human cancer using products with any engineered primary TCR alpha/beta T cells and non-exclusively in the field of treatment, prevention or diagnosis of any human cancer using products with certain other engineered immune cells worldwide, and in November 2022, we entered into a Collaboration and License Agreement with Ionis to research, develop and commercialize investigational medicines using genome editing technologies. In October 2021, we entered into the Moderna Agreement with Moderna, focused on advancing new genome editing system forin vivo human therapeutic applications, and in April 2024, we and Moderna mutually terminated the Moderna Agreement. Refer to Note 7 in our condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for additional information related to the terms of the agreements between us and our collaborators and Note 12 in our condensed consolidated financial statements included elsewhere in this Quarterly Report on Form 10-Q for additional information related to the termination of the Moderna Agreement.

Previous wording

To date, all of our revenue consists of collaboration revenue, earned from collaboration agreements with Moderna (prior to the termination of the Moderna Agreement), Ionis and Affini-T. These agreements may include the following types of promised goods or services: (i) grants of licenses; (ii) performance of research and development services and (iii) participation on joint research and/or development committees. They also may include options to obtain licenses to our intellectual property or to extend the term of the research activities. Our revenues under such collaboration agreements were $11.2 million and $8.7 million for the three months ended March 31, 2024 and 2023, respectively. We expect to recognize $15.9 million of deferred revenue in the second quarter of 2024 as a result of the Termination Agreement with Moderna and expect no further collaboration revenue under the Moderna Agreement.

Current wording

To date, all of our revenue consists of collaboration revenue, earned from collaboration agreements with Moderna (prior to the termination of the Moderna Agreement), Ionis and Affini-T. These agreements may include the following types of promised goods or services: (i) grants of licenses; (ii) performance of research and development services and (iii) participation on joint research and/or development committees. They also may include options to obtain licenses to our intellectual property or to extend the term of the research activities. Our revenues under such collaboration agreements were $20.0 million and $31.2 million for the three and six months ended June 30, 2024, respectively, and $11.3 million and $20.0 million for the three and six months ended June 30, 2023, respectively.

Previous wording

Total other income, net includes interest income from our investments in available-for-sale marketable securities.

Current wording

Total other income, net, includes interest income from our investments in available-for-sale marketable securities and changes in the fair value of our investment in Affini-T.

Previous wording

Comparison of the Three Months Ended March 31, 2024 and 2023

Current wording

Comparison of the Three and Six Months Ended June 30, 2024 and 2023

Previous wording

Our revenue consists of collaboration revenue recognized under our agreements with Moderna (prior to the termination of the Moderna Agreement), Affini-T and Ionis. We recognize revenue as the performance obligations are satisfied. Collaboration revenue increased by $2.5 million, from $8.7 million for the three months ended March 31, 2023 to $11.2 million for the three months ended March 31, 2024. The increase in collaboration revenue for the three months ended March 31, 2024, was primarily driven by a $4.4 million increase in revenue related to the Ionis Agreement as we performed more services and collaboration activities progressed, offset by a $1.5 million decrease in revenue related to the Moderna Agreement and a $0.4 million decrease in revenue related to the Affini-T Agreement. After recognition of the deferred revenue expected in the second quarter of 2024 as a result of the Termination Agreement with Moderna, we expect that collaboration revenues will decrease in the future.

Current wording

Our revenue consists of collaboration revenue recognized under our agreements with Moderna (prior to the termination of the Moderna Agreement), Affini-T and Ionis. We recognize revenue as the performance obligations are satisfied. Collaboration revenue increased by $8.7 million, from $11.3 million for the three months ended June 30, 2023 to $20.0 million for the three months ended June 30, 2024 and increased by $11.2 million, from $20.0 million for the six months ended June 30, 2023 to $31.2 million for the six months ended June 30, 2024. The increase in collaboration revenue for the three months ended June 30, 2024 was primarily driven by a $11.4 million increase in revenue related to the Moderna Agreement mainly due to the recognition of all remaining deferred revenue of $15.9 million resulting from the Termination Agreement, offset by a $1.7 million decrease in revenue related to the Ionis Agreement and a $1.0 million decrease in revenue related to the Affini-T Agreement. The increase in collaboration revenue for the six months ended June 30, 2024 was primarily driven by a $9.9 million increase in revenue related to the Moderna Agreement mainly due to the recognition of all remaining deferred revenue during the six months ended June 30, 2024 and a $2.7 million increase in revenue related to the Ionis Agreement as we performed more services, offset by a $1.4 million decrease in revenue related to the Affini-T Agreement.

Previous wording

Employee-related expenses increased by $7.2 million, including a $3.7 million increase in stock-based compensation expense related to increased headcount and a one-time acceleration of stock-based compensation expense related to profits interests units that were canceled without a concurrent grant of a replacement award during the Reorganization and were accounted for as a repurchase for no consideration. Laboratory materials and supplies increased by $1.3 million due to significant expansion of our research and development operations. Facilities and allocated overhead, including rent, repairs and maintenance costs, common facilities and information technology related expenses allocated to research and development increased by $0.4 million mainly related to a $0.4 million increase in depreciation expense as we continue investing in our lab and manufacturing capabilities. Other research and development and consulting costs increased by $2.4 million mainly due to external research and development costs to support our research and pre-clinical development activities.

Current wording

Employee-related expenses increased by $3.7 million and $10.9 million during the three and six months ended June 30, 2024, respectively, including a $1.9 million and $5.7 million increase, respectively, in stock-based compensation expense related to increased headcount and issuance of annual equity awards to existing employees, in addition to a one-time acceleration of stock-based compensation expense related to profits interests units that were canceled without a concurrent grant of a replacement award during the Reorganization and were accounted for as a repurchase for no consideration during the six months ended June 30, 2024. Laboratory materials and supplies increased by $2.1 million and $3.5 million during the three and six months ended June 30, 2024, respectively, due to expansion of our research and development operations. Facilities and allocated overhead, including rent, repairs and maintenance costs, common facilities and information technology related expenses allocated to research and development increased by $1.4 million and $1.8 million during the three and six months ended June 30, 2024, respectively. Other research and development and consulting costs decreased by $1.6 million during the three months ended June 30, 2024 and increased by $0.7 million during the six months ended June 30, 2024, mainly due to the timing of external research and development costs to support our research and preclinical development activities.

Previous wording

Total other income, net, decreased by $0.1 million, from $4.0 million for the three months ended March 31, 2023 to $3.9 million for the three months ended March 31, 2024.

Current wording

Total other income, net, decreased by $2.9 million, from $6.9 million for the three months ended June 30, 2023 to $3.9 million for the three months ended June 30, 2024 and decreased by $3.0 million, from $10.9 million for the six months ended June 30, 2023 to $7.8 million for the six months ended June 30, 2024. The decrease in other income, net, for both the three and six months ended June 30, 2024 was primarily due to a change in the fair value of our long term investment in Affini-T which was remeasured to fair value during the three and six months ended June 30, 2023.

Previous wording

Provision for income taxes decreased by $2.2 million, from $2.2 million for the three months ended March 31, 2023 to zero for the three months ended March 31, 2024. Income tax expense for the three months ended March 31, 2023 was mainly due to our taxable income related to an upfront payment received under the Ionis Agreement and capitalization of research and development expenses under the Internal Revenue Code Section 174 (“Section 174”).

Current wording

Provision for income taxes decreased by $4.1 million and $6.3 million for the three and six months ended June 30, 2024, respectively, from a provision for income taxes of $1.9 million and $4.1 million for three and six months ended June 30, 2023, respectively, to a benefit for income taxes of $2.2 million for both the three and six months ended June 30, 2024. The benefit for income taxes for the three and six months ended June 30, 2024 was due to our intention to elect to carry back the 2024 research and development credit to the prior year. The provision for income taxes for the three and six months ended June 30, 2023 was mainly due to our taxable income related to an upfront payment received under the Ionis Agreement and capitalization of research and development expenses under the Internal Revenue Code Section 174 (“Section 174”).

Previous wording

We have incurred significant operating losses since inception and we expect to continue to incur substantial losses for the foreseeable future. Our net losses were $68.3 million and $43.6 million for the years ended December 31, 2023 and 2022, respectively, and $25.1 million and $16.1 million for the three months ended March 31, 2024 and 2023, respectively. As of March 31, 2024, we had an accumulated deficit of $170.1 million.

Current wording

We have incurred significant operating losses since inception and we expect to continue to incur substantial losses for the foreseeable future. Our net losses were $68.3 million and $43.6 million for the years ended December 31, 2023 and 2022, respectively, and $35.9 million and $29.1 million for the six months ended June 30, 2024 and 2023, respectively. As of June 30, 2024, we had an accumulated deficit of $180.8 million.

Previous wording

As of March 31, 2024, we had $327.4 million in cash, cash equivalents and available-for-sale marketable securities. We believe that our existing cash, cash equivalents and available-for-sale marketable securities will be sufficient to fund our current operating plan for at least the next 12 months. Based on our current operating plan, we estimate that our existing cash, cash equivalents and available-for-sale marketable securities will be sufficient to fund our projected operating expenses and capital expenditure requirements into 2027, and provide cash runway to support 2 INDs and 2 additional development candidate nominations. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” and “Risk Factors—Risks Related To Our Financial Position and Need for Additional Capital.” We expect that we will require additional funding to: continue our current research development activities; develop, maintain, expand and protect our intellectual property portfolio; further develop our platform; and hire additional research, clinical and scientific personnel. If we receive regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, sales, marketing and distribution, depending on where we choose to commercialize our products.

Current wording

As of June 30, 2024, we had $299.9 million in cash, cash equivalents and available-for-sale marketable securities. We believe that our existing cash, cash equivalents and available-for-sale marketable securities will be sufficient to fund our current operating plan for at least the next 12 months. Based on our current operating plan, we estimate that our existing cash, cash equivalents and available-for-sale marketable securities will be sufficient to fund our projected operating expenses and capital expenditure requirements into 2027. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “Liquidity and Capital Resources” and “Risk Factors—Risks Related To Our Financial Position and Need for Additional Capital.” We expect that we will require additional funding to: continue our current research development activities; develop, maintain, expand and protect our intellectual property portfolio; further develop our platform; and hire additional research, clinical and scientific personnel. If we receive regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, sales, marketing and distribution, depending on where we choose to commercialize our products.

Previous wording

Net cash used in operating activities was $29.9 million for the three months ended March 31, 2024 and consisted primarily of our net loss of $25.1 million and changes in our net operating assets and liabilities of $10.9 million, partially offset by net non-cash charges of $6.2 million. The net change in operating assets and liabilities consisted primarily of a decrease of $10.4 million in deferred revenue as we recognized revenue under our collaboration agreements, a $3.0 million decrease in accrued expenses and other current liabilities primarily related to payout of the 2023 annual bonus, and a $0.9 million increase in prepaid expenses and other assets, offset by an increase of $3.2 million in accounts payable due to the timing of payments to our vendors. The net non-cash charges consisted primarily of $5.1 million in stock-based compensation expense, $1.1 million in non-cash lease expense, and $1.3 million of depreciation expense, partially offset by $1.2 million in amortization of discounts on available-for-sale marketable securities.

Current wording

Net cash used in operating activities was $56.2 million for the six months ended June 30, 2024 and consisted primarily of our net loss of $35.9 million and changes in our net operating assets and liabilities of $31.7 million, partially offset by net non-cash charges of $11.4 million. The net change in operating assets and liabilities consisted primarily of a decrease of $29.4 million in deferred revenue as we recognized revenue under our collaboration agreements, a $3.3 million decrease in income tax payable due to payment of our 2023 income tax liability and a decrease of $1.3 million in other non-current liabilities, offset by an increase of $1.7 million in accounts payable due to the timing of payments to our vendors. The net non-cash charges consisted primarily of $9.6 million in stock-based compensation expense, $2.6 million of depreciation expense, and $2.3 million in non-cash lease expense, partially offset by $3.2 million in amortization of discounts on available-for-sale marketable securities.

Previous wording

Net cash used in operating activities for the three months ended March 31, 2023 was $21.0 million and consisted primarily of our net loss of $16.1 million and changes in our net operating assets and liabilities of $5.0 million, partially offset by net non-cash charges of $0.1 million. The changes in our net operating assets and liabilities primarily consisted of a decrease of $7.8 million in deferred revenue as we recognized revenue under our collaboration agreements, and a decrease of $1.3 million in accrued expenses and other current liabilities, partially offset by a $1.9 million increase in income tax payable, a $1.3 million decrease in contract assets, and a $1.2 million increase in accounts payable. The net non-cash charges consisted primarily of $1.0 million in non-cash lease expense, $0.8 million of depreciation expense, and $0.5 million in stock-based compensation expense, offset by $2.2 million in amortization of the discount on our available-for-sale marketable securities.

Current wording

Net cash used in operating activities for the six months ended June 30, 2023 was $47.1 million and consisted primarily of our net loss of $29.1 million and changes in our net operating assets and liabilities of $15.1 million, partially offset by net non-cash income of $2.8 million. The changes in our net operating assets and liabilities consisted primarily of a decrease of $16.2 million in deferred revenue as we recognized revenue under our collaboration agreements, and an increase of $2.3 million in accounts receivable, partially offset by a $1.3 million decrease in contract assets and a $1.2 million increase in income tax payable. The net non-cash income consisted primarily of $4.5 million in amortization of the discount on our available-for-sale marketable securities and $2.9 million increase in the fair value of our investments in Affini-T, offset by $2.0 million in non-cash lease expense, $1.9 million of depreciation expense, and $1.2 million in stock-based compensation expense.

Previous wording

Net cash used in investing activities for the three months ended March 31, 2024 was $94.7 million due to net purchases of available-for-sale marketable securities of $93.8 million and purchases of property and equipment of $0.9 million

Current wording

Net cash used in investing activities for the six months ended June 30, 2024 was $107.8 million due to net purchases of available-for-sale marketable securities of $106.2 million and purchases of property and equipment of $1.6 million.

Previous wording

Net cash used in investing activities for the three months ended March 31, 2023 was $72.1 million due to net purchases of available-for-sale marketable securities of $69.4 million and purchases of property and equipment of $2.7 million.

Current wording

Net cash used in investing activities for the six months ended June 30, 2023 was $90.8 million due to net purchases of available-for-sale marketable securities of $85.0 million and purchases of property and equipment of $5.8 million.

Previous wording

Net cash provided by financing activities for the three months ended March 31, 2024 was $86.5 million due to net proceeds from the issuance of our common stock in our IPO, net of issuance costs paid during the period.

Current wording

Net cash provided by financing activities for the six months ended June 30, 2024 was $84.5 million due to net proceeds from the issuance of our common stock in our IPO, net of issuance costs paid during the period.

Previous wording

Net cash provided by financing activities for the three months ended March 31, 2023 was $4.3 million due to net proceeds from the issuance of our Series B-1 redeemable convertible preferred stock.

Current wording

Net cash provided by financing activities for the six months ended June 30, 2023 was $4.3 million primarily due to net proceeds from the issuance of our Series B-1 redeemable convertible preferred stock.

Previous wording

Our material cash requirements include our contractual obligations for our leased office and laboratory space under three lease agreements and one vivarium lease agreement. During the three months ended March 31, 2024, there were no material changes outside the ordinary course of our business to our material cash requirements described under “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 27, 2024.

Current wording

Our material cash requirements include our contractual obligations for our leased office and laboratory space under three lease agreements and one vivarium lease agreement. During the six months ended June 30, 2024, there were no material changes outside the ordinary course of our business to our material cash requirements described under “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 27, 2024.

Previous wording

During the three months ended March 31, 2024, there were no material changes to our critical accounting estimates or in the methodology used for estimates from those described in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K for the year ended December 31, 2023.

Current wording

During the six months ended June 30, 2024, there were no material changes to our critical accounting estimates or in the methodology used for estimates from those described in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included in our Annual Report on Form 10-K for the year ended December 31, 2023.