Revolution Medicines Inc

Previous wording

We are planning a global, randomized Phase 3 registrational trial of RMC-6236 in the 2L treatment of patients with metastatic PDAC, which we call the RASolute 302 study. In the RASolute 302 study, we plan to randomize patients in a 1:1 ratio to receive either RMC-6236 at a dose of 300 mg daily or the investigator’s choice of chemotherapy. The RASolute 302 study is further anticipated to have a nested trial design allowing for a hierarchical sequence of statistical analysis, with patients with tumors harboring RAS G12X mutations serving as the core population which will be tested first and all enrolled patients serving as the secondary population. We believe this nested design and hierarchical testing increases the probably of trial success based on the core population while creating an opportunity to gain approval for a broader population. Patients in the RASolute 302 study are expected to be evaluated for the dual primary endpoints of PFS and OS, with secondary endpoints including ORR and quality of life measures. The Company’s current planned trial design and dose selection for the RASolute 302 study are based on initial feedback from the U.S. Food and Drug Administration (FDA), including supportive discussions on high level trial design and dose, but are subject to finalization pending the Company’s final protocol submission and FDA review. We currently expect to initiate the RASolute 302 study in the second half of 2024.

Current wording

A global, randomized Phase 3 registrational trial of RMC-6236 in the second-line (2L) treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC), which we call the RASolute 302 study, is ongoing. In the RASolute 302 study, we are randomizing patients in a 1:1 ratio to receive either RMC-6236 at a dose of 300 mg daily or the investigator’s choice of chemotherapy. The RASolute 302 study has a nested trial design allowing for a hierarchical sequence of statistical analysis, with patients with tumors harboring RAS G12X mutations serving as the core population which will be tested first and all enrolled patients serving as the secondary population. We believe this nested design and hierarchical testing increases the probability of trial success based on the core population while creating an opportunity to gain approval for a broader population. Patients in the RASolute 302 study will be evaluated for the dual primary endpoints of progression-free survival (PFS) and overall survival (OS) in the core population, with secondary endpoints including PFS and OS in the secondary population and objective response rate (ORR) and quality of life measures across all measures. Readout of RASolute 302 will be event-driven after the study is fully enrolled.

Previous wording

We are also planning a global, randomized Phase 3 registrational trial comparing RMC-6236 against docetaxel in patients with RAS-mutated NSCLC who have been treated with immunotherapy and platinum-containing chemotherapy. The study design for this planned trial is subject to change based on regulatory authority feedback. We currently expect to initiate this study in the fourth quarter of 2024.

Current wording

We are also planning a global, randomized Phase 3 registrational trial comparing RMC-6236 against docetaxel in patients with RAS-mutated non-small cell lung cancer (NSCLC) who have been treated with immunotherapy and platinum-containing chemotherapy. The study design for this planned trial is subject to change based on regulatory authority feedback. We currently expect to reach regulatory alignment and initiate this study in the first quarter of 2025.

Previous wording

On October 22, 2023, we reported interim safety and anti-tumor activity data for dose levels of 80 mg daily and above from the RMC-6236-001 study as of an October 12, 2023 data cut-off date. These data demonstrated that RMC-6236 was generally well tolerated across the dose levels analyzed as of the cut-off date. These data also demonstrated preliminary evidence of clinical activity in pancreatic ductal adenocarcinoma (PDAC) patients and non-small cell lung cancer (NSCLC) patients.

Current wording

On October 22, 2023, we reported interim safety and anti-tumor activity data for dose levels of 80 mg daily and above from the RMC-6236-001 study as of an October 12, 2023 data cut-off date. These data demonstrated that RMC-6236 was generally well tolerated across the dose levels analyzed as of the cut-off date. These data also demonstrated preliminary evidence of clinical activity in PDAC patients and NSCLC patients.

Previous wording

On January 9, 2024, we reported that, with additional follow-up after the October 2023 data report described above, the profile of RMC-6236 remained relatively consistent with the description in the October 2023 report, the objective response rate (ORR) for both PDAC and NSCLC patients had improved, and the disease control rate (DCR) remained consistent.

Current wording

On January 9, 2024, we reported that, with additional follow-up after the October 2023 data report described above, the profile of RMC-6236 remained relatively consistent with the description in the October 2023 report, the ORR for both PDAC and NSCLC patients had improved, and the disease control rate (DCR) remained consistent.

Previous wording

Also at the AACR Annual Meeting 2024, we reported individual case studies from the RMC-6236-001 study that showed examples of objective responses to RMC-6236 in patients with tumor types beyond PDAC or NSCLC, specifically patients with melanoma and with colorectal cancer (CRC). We believe that these observations may support further development opportunities for RMC-6236.

Current wording

Also at the AACR Annual Meeting 2024, we reported individual case studies from the RMC-6236-001 study that showed examples of objective responses to RMC-6236 in patients with tumor types beyond PDAC or NSCLC, specifically patients with melanoma and with colorectal cancer (CRC).

Previous wording

On July 15, 2024, we reported updated clinical safety, tolerability and activity data from the RMC-6236-001 study, as of a May 11, 2024 cut-off date (the Data Cutoff Date), for patients with previously treated PDAC. In the RMC-6236-001 study, a total of 127 patients with PDAC treated across dose cohorts ranging from 160 mg daily to 300 mg daily were evaluated for safety and tolerability as of the Data Cutoff Date. As of the Data Cutoff Date, approximately 22% of these patients experienced a Grade 3 or higher treatment-related adverse event (TRAE), and 96% of these patients experienced a TRAE of any grade. The most common TRAEs that were observed were rash and gastrointestinal-related toxicities. We also reported TRAEs that led to dose modifications, where we observed dose interruption and/or reduction for 28% of these patients, but no TRAEs leading to discontinuation.

Current wording

In the RMC-6236-001 study, a total of 127 patients with PDAC treated across dose cohorts ranging from 160 mg daily to 300 mg daily were evaluated for safety and tolerability as of the RMC-6236 Data Cutoff Date. As of the RMC-6236 Data Cutoff Date, approximately 29% of these patients experienced a Grade 3 or higher treatment-related adverse event (TRAE), and 98% of these patients experienced a TRAE of any grade. The most common TRAEs that were observed were rash and gastrointestinal (GI)-related toxicities. One Grade 4 TRAE (platelet count decreased) was observed. No Grade 5 TRAEs were observed. We also reported the TRAEs leading to dose modifications, where we observed dose interruption and/or reduction for 35% of these patients, but no TRAEs that resulted in treatment discontinuation.

Previous wording

We also reported preliminary progression-free survival (PFS) data as of the Data Cutoff Date for patients with metastatic PDAC treated with RMC-6236 in the second-line (2L) setting across dose cohorts ranging from 160 mg daily to 300 mg daily. As of the Data Cutoff Date, the median PFS for these patients with tumors harboring KRAS G12X mutations was 8.1 months (95% confidence interval (CI): 5.9 months, not estimable), and the median PFS for these patients with tumors harboring G12X, G13X and Q61X mutations was 7.6 months (95% CI: 5.3 months, not estimable). We also reported preliminary PFS data as of the Data Cutoff Date for patients with tumors harboring KRAS G12X mutations who were treated with RMC-6236 in the third-line or later (3L+) setting across dose cohorts ranging from 160 mg daily to 300 mg daily. As of the Data Cutoff Date, the median PFS for these patients was 4.2 months (95% CI: 4.1 months, 6.4 months).

Current wording

We also reported updated preliminary PFS results as of the RMC-6236 Data Cutoff Date for patients with metastatic PDAC treated with RMC-6236 in the second-line or later (2L+) setting across dose cohorts ranging from 160 mg daily to 300 mg daily. As of the RMC-6236 Data Cutoff Date, the median PFS for patients treated with RMC-6236 in the 2L setting with tumors harboring KRAS G12X mutations was 8.5 months (95% confidence interval (CI): 5.3 – 11.7 months), and for these patients with tumors harboring G12, G13 or Q61 mutations was 7.6 months (95% CI: 5.9 – 11.1 months). As of the RMC-6236 Data Cutoff Date, the median PFS for these patients treated with RMC-6236 in the third-line or later (3L+) setting with tumors harboring KRAS G12X mutations was 4.4 months (95% CI: 4.2 – 6.4 months), and for these patients with tumors harboring G12, G13 or Q61 mutations was 4.4 months (95% CI: 4.1 – 5.7 months).

Previous wording

We also reported interim observed overall survival, or OS, data as of the Data Cutoff Date for patients with metastatic PDAC who were treated with RMC-6236 in the 2L setting across dose cohorts ranging from 160 mg daily to 300 mg daily. The interim OS as of the Data Cutoff Date for these patients with tumors harboring KRAS G12X mutations was not estimable (95% CI: 8.5 months, not estimable) and for patients with tumors harboring G12X, G13X and Q61X mutations was also not estimable (95% CI: 8.5 months, not estimable).

Current wording

We also reported preliminary OS data as of the RMC-6236 Data Cutoff Date for patients with metastatic PDAC who were treated with RMC-6236 in the 2L setting across dose cohorts ranging from 160 mg daily to 300 mg daily. The median OS for these patients with tumors harboring KRAS G12X mutations was 14.5 months (95% CI: 8.8 months, not estimable) and the median OS for these patients with tumors harboring G12, G13 or Q61 mutations was also 14.5 months (95% CI: 8.8 months, not estimable). As of the RMC-6236 Data Cutoff Date, the OS rate at 6 months was 89% (95% CI: 70–97%) for these patients with tumors harboring KRAS G12X mutations and was 91% (95% CI: 77–96%) for these patients with tumors harboring G12, G13 or Q61 mutations.

Previous wording

In addition, we reported best percentage change in tumor size from baseline for patients with PDAC treated with RMC-6236 in the 2L or later (2L+) setting as of the Data Cutoff Date. The ORR for these patients who received the first dose of RMC-6236 at least 14 weeks prior to the Data Cutoff Date was 20% for patients with tumors harboring KRAS G12X mutations and was 21% for patients with tumors harboring G12X, G13X and Q61X mutations. The ORR for these patients who received the first dose of RMC-6236 at least 20 weeks prior to the Data Cutoff Date was 27% for patients with tumors harboring KRAS G12X mutations and was 26% for patients with tumors harboring G12X, G13X and Q61X mutations. The DCR for these patients who received the first dose of RMC-6236 at least 14 weeks prior to the Data Cutoff Date was 87% for patients with tumors harboring KRAS G12X mutations and was 88% for patients with tumors harboring G12X, G13X and Q61X mutations.

Current wording

We also reported best percentage change in tumor size from baseline for patients with metastatic PDAC with tumors harboring KRAS G12X mutations treated with RMC-6236 in the 2L+ setting as of the RMC-6236 Data Cutoff Date. The ORR for these patients who received the first dose of RMC-6236 at least 14 weeks prior to the RMC-6236 Data Cutoff Date was 29% for patients in the 2L setting and was 22% for patients in the 3L+ setting. The disease control rate (DCR) for these patients who received the first dose of RMC-6236 at least 14 weeks prior to the RMC-6236 Data Cutoff Date was 91% for these patients in the 2L setting and was 89% for these patients in the 3L+ setting.

Previous wording

Based on our observations from the RMC-6236-001 study and our preclinical observations, we believe there is a potential opportunity to evaluate RMC-6236 in earlier lines of therapy and are currently evaluating several exploratory combination regimens that include RMC-6236 in order to assess the potential for development in these settings. These combinations include RMC-6236 with pembrolizumab, RMC-6236 with RMC-6291, and RMC-6236 with standard of care chemotherapy agents. We currently expect to disclose initial clinical pharmacokinetic (PK), safety, tolerability and activity data for the combination of RMC-6236 with pembrolizumab and for the combination of RMC-6236 with RMC-6291 in the fourth quarter of 2024.

Current wording

RMC-6236 with pembrolizumab, RMC-6236 with RMC-6291, RMC-6236 with RMC-9805 and RMC-6236 with standard of care chemotherapy agents. We currently expect to disclose initial clinical pharmacokinetic (PK), safety, tolerability and activity data for the combination of RMC-6236 with pembrolizumab and for the combination of RMC-6236 with RMC-6291 in the fourth quarter of 2024.

Previous wording

In addition, an exploratory combination study of RMC-9805 with RMC-6236 is ongoing.

Current wording

We believe that this preliminary safety and clinical activity data as of the RMC-9805 Data Cutoff Date support our ongoing development of RMC-9805 as a single agent and in combination with other therapies, including with RMC-6236. An exploratory combination study of RMC-9805 with RMC-6236 is ongoing.

Previous wording

RMC-0708 is designed as a RAS(ON) oral Q61H-selective inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other

Current wording

RMC-0708 is designed as a RAS(ON) oral Q61H-selective inhibitor. It is designed to exhibit picomolar potency for suppressing RAS pathway signaling and growth of RAS Q61H-bearing cancer cells and is engineered for selective inhibition of RAS Q61H over other RAS isoforms via non-covalent binding interactions. Clinical development of RMC-0708 is subject to our continuing assessment of our portfolio priorities.

Previous wording

We reported additional interim data from the ongoing dose-escalation portion of the RMC-5552-001 study in October 2023 as of a September 4, 2023 data cut-off date. These data further support our previous observations that RMC-5552 was acceptably tolerated at doses that have demonstrated meaningful anti-tumor activity in clinical studies, while largely avoiding well-described toxicities associated with mTORC2 inhibition, such as hyperglycemia.

Current wording

We reported interim data from the ongoing dose-escalation portion of the RMC-5552-001 study in October 2023 as of a September 4, 2023 data cut-off date. These data further support our previous observations that RMC-5552 was acceptably tolerated at doses that have demonstrated meaningful anti-tumor activity in clinical studies, while largely avoiding well-described toxicities associated with mTORC2 inhibition, such as hyperglycemia.

Previous wording

As a result of the EQRx Acquisition, we acquired approximately $1.1 billion in net cash, cash equivalents and marketable securities after deducting estimated EQRx wind-down and transaction costs.

Current wording

As a result of the EQRx Acquisition, we acquired $1.1 billion in net cash, cash equivalents and marketable securities after deducting estimated EQRx wind-down and transaction costs.

Previous wording

costs related to production of clinical and preclinical materials, including fees paid to contract manufacturers;

Current wording

costs related to the production of preclinical, clinical and pre-launch materials, including fees paid to contract manufacturers;

Previous wording

Comparison of the three and six months ended June 30, 2024 and 2023

Current wording

Comparison of the three and nine months ended September 30, 2024 and 2023

Previous wording

Collaboration revenue consisted of revenue under the Sanofi Agreement, which terminated in June 2023. Collaboration revenue decreased by $3.8 million to zero during the three months ended June 30, 2024 compared to the same period in 2023. Collaboration revenue decreased by $10.8 million to zero during the six months ended June 30, 2024 compared to the same period in 2023. The decrease in collaboration revenue in 2024 was a result of the termination of the Sanofi Agreement.

Current wording

Collaboration revenue consisted of revenue under the Sanofi Agreement, which terminated in June 2023. Collaboration revenue decreased by $10.8 million to zero during the nine months ended September 30, 2024 compared to the same period in 2023. The decrease in collaboration revenue in 2024 was a result of the termination of the Sanofi Agreement.

Previous wording

Our research and development efforts during the three and six months ended June 30, 2024 and 2023 were focused on our clinical development programs and our preclinical programs. The following table sets forth the components of our research and development expenses for the periods indicated:

Current wording

Our research and development efforts during the three and nine months ended September 30, 2024 and 2023 were focused on our clinical development programs and our preclinical programs. The following table sets forth the components of our research and development expenses for the periods indicated:

Previous wording

Research and development expenses increased by $37.0 million, or 38%, during the three months ended June 30, 2024 compared to the same period in 2023. The increase in research and development expenses during the three months ended June 30, 2024 was primarily due to a $10.0 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $8.6 million increase in RMC-6291 expenses, primarily attributable to higher clinical trial expenses; a $6.1 million increase in preclinical research portfolio expenses; a $5.1 million increase in stock-based compensation; a $5.0 million increase in RMC-6236 expenses, primarily attributable to clinical trial expenses; a $3.9 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; and a $1.9 million increase in RMC-9805 expenses primarily attributable to clinical trial expenses; partially offset by a $3.6 million decrease in other RAS companion inhibitor program expenses.

Current wording

September 30, 2024 was primarily due to a $21.7 million increase in RMC-6236 expenses, primarily attributable to clinical trial expenses; a $9.5 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $5.2 million increase in stock-based compensation; a $4.3 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; a $3.7 million increase in RMC-9805 expenses, primarily attributable to clinical trial expenses; and a $1.2 million increase in RMC-6291 expenses, primarily attributable to higher clinical trial expenses; partially offset by a $1.4 million decrease in other RAS companion inhibitor program expenses.

Previous wording

Research and development expenses increased by $86.0 million, or 52%, during the six months ended June 30, 2024 compared to the same period in 2023. The increase in research and development expenses during the six months ended June 30, 2024 was primarily due to a $22.5 million increase in RMC-6236 expenses, primarily attributable to clinical trial expenses; a $20.0 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $13.5 million increase in our preclinical research portfolio expenses; a $12.8 million increase in RMC-6291 expenses, primarily attributable to higher clinical trial expenses; a $9.7 million increase in stock-based compensation; a $7.6 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; and a $6.3 million increase in RMC-9805 expenses primarily attributable to clinical trial expenses; partially offset by a $6.4 million decrease in other RAS companion inhibitor program expenses.

Current wording

Research and development expenses increased by $129.5 million, or 47%, during the nine months ended September 30, 2024 compared to the same period in 2023. The increase in research and development expenses during the nine months ended September 30, 2024 was primarily due to a $44.1 million increase in RMC-6236 expenses, primarily attributable to clinical trial expenses; a $29.0 million increase in salaries and other employee-related expenses due to increased headcount to support our research and development programs; a $14.9 million increase in stock-based compensation; a $14.0 million increase in RMC-6291 expenses, primarily attributable to higher clinical trial expenses; a $13.4 million increase in our preclinical research portfolio expenses; a $11.8 million increase in other research and development expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; and a $10.1 million increase in RMC-9805 expenses primarily attributable to clinical trial expenses; partially offset by a $7.8 million decrease in other RAS companion inhibitor program expenses.

Previous wording

General and administrative expenses increased by $16.7 million, or 60%, during the six months ended June 30, 2024 compared to the same period in 2023. The increase in general and administrative expenses during the six months ended June 30, 2024 was primarily due to a $5.0 million increase in salaries and other employee-related expenses due to increased headcount; a $3.6 million increase in stock-based compensation expense; a $3.4 million increase in commercial preparation activities; a $2.3 million increase in facilities and other allocated expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount and a $1.7 million increase in legal and accounting fees.

Current wording

General and administrative expenses increased by $8.4 million, or 54%, during the three months ended September 30, 2024 compared to the same period in 2023. The increase in general and administrative expenses during the three months ended September 30, 2024 was primarily due to a $1.9 million increase in salaries and other employee-related expenses due to increased headcount; a $1.9 million increase in stock-based compensation expense; a $1.8 million increase in commercial preparation activities; a $1.2 million increase in legal and accounting fees; and a $1.1 million increase in facilities and other allocated expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount.

Previous wording

General and administrative expenses increased by $7.1 million, or 48%, during the three months ended June 30, 2024 compared to the same period in 2023. The increase in general and administrative expenses during the three months ended June 30, 2024 was primarily due to a $1.9 million increase in salaries and other employee-related expenses due to increased headcount; a $1.9 million increase in commercial preparation activities and a $1.7 million increase in stock-based compensation expense.

Current wording

General and administrative expenses increased by $25.7 million, or 59%, during the nine months ended September 30, 2024 compared to the same period in 2023. The increase in general and administrative expenses during the nine months ended September 30, 2024 was primarily due to a $7.5 million increase in salaries and other employee-related expenses due to increased headcount; a $5.5 million increase in stock-based compensation expense; a $5.2 million increase in commercial preparation activities; a $3.4 million increase in facilities and other allocated expenses as a result of higher rent, utilities and information technology expenses associated with increased headcount; a $2.8 million increase in legal and accounting fees; and a $1.3 million increase in other administrative expenses.

Previous wording

Interest income increased by $11.0 million and $27.7 million during the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023 due to a larger cash, cash equivalents and marketable securities balance and higher interest rates.

Current wording

Interest income increased by $9.5 million and $37.2 million during the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023 due to a larger cash, cash equivalents and marketable securities balance and higher interest rates.

Previous wording

Other income (expense) increased by less than $0.1 million and decreased by $2.8 million during the three and six months ended June 30, 2024, respectively, compared to the same periods in 2023 due to a $2.8 million impairment in the first quarter of 2024 of a long term asset acquired as part of the EQRx Acquisition.

Current wording

Other income increased by $0.3 million and decreased by $2.5 million during the three and nine months ended September 30, 2024, respectively, compared to the same periods in 2023. The increase for the nine months ended September 30, 2024 was due to a $2.8 million impairment of a long term asset acquired as part of the EQRx Acquisition in the first quarter of 2024 offset by a change in the fair value of warrant liabilities and contingent earn-out shares acquired as part of the EQRx Acquisition.

Previous wording

In November 2021, we entered into a sales agreement with Cowen and Company, LLC (Cowen) to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $250 million, through an at-the-market equity offering program (the 2021 ATM) under which Cowen agreed to act as our sales agent. Since then, we have sold an aggregate of 6,502,078 shares of our common stock under the 2021 ATM resulting in gross proceeds to us of $186.0 million. During the three and six months ended June 30, 2024, we did not sell any shares of our common stock under the ATM. In August 2024, we terminated the 2021 ATM and entered into a new sales agreement with TD Securities (USA) LLC (TD Cowen) to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $500 million, through an at-the-market equity offering program (the 2024 ATM) under which TD Cowen agreed to act as our sales agent.

Current wording

In November 2021, we entered into a sales agreement with Cowen and Company, LLC, an affiliate of TD Securities (USA) LLC (TD Cowen), as amended in March 2024, to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $250 million, through an at-the-market equity offering program (the 2021 ATM). We have sold an aggregate of 6,502,078 shares of our common stock under the 2021 ATM resulting in gross proceeds to us of $186.0 million. During the three and nine months ended September 30, 2024, we sold an aggregate of 1,294,050 shares of common stock under the 2021 ATM, resulting in gross proceeds of $60.8 million. In August 2024, we terminated the 2021 ATM and entered into a new sales agreement with TD Cowen to sell shares of our common stock, from time to time, with aggregate gross proceeds of up to $500 million, through an at-the-market equity offering program (the 2024 ATM). Through September 30, 2024, we have sold an aggregate of 333,526 shares of common stock under the 2024 ATM, resulting in gross proceeds of $15.3 million.

Previous wording

As of June 30, 2024, we had $1.6 billion in cash, cash equivalents and marketable securities.

Current wording

As of September 30, 2024, we had $1.5 billion in cash, cash equivalents and marketable securities.

Previous wording

As of June 30, 2024, we had an accumulated deficit of $1.4 billion. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our product candidates and our pre-clinical research portfolio, and to a lesser extent, general and administrative expenditures. We expect our expenses to continue to increase in connection with our ongoing activities, particularly as we continue to advance our product candidates and pre-clinical research portfolio.

Current wording

As of September 30, 2024, we had an accumulated deficit of $1.5 billion. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our product candidates and our pre-clinical research portfolio, and to a lesser extent, general and administrative expenditures. We expect our expenses to continue to increase in connection with our ongoing activities, particularly as we continue to advance our product candidates and pre-clinical research portfolio.

Previous wording

During the six months ended June 30, 2024, cash used in operating activities of $288.7 million was attributable to a net loss of $249.2 million and a net change of $52.0 million in our operating assets and liabilities and $12.5 million in non-cash charges. The change in operating assets and liabilities was primarily due to a $33.0 million decrease in accounts payable; an $8.9 million increase in prepaid expenses and other current assets; a $6.6 million decrease in accrued expenses and other current liabilities; and an increase in other noncurrent assets by $4.0 million, offset by a $1.3 million decrease in accounts receivable. The non-cash charges primarily consisted of stock-based compensation expense of $36.0 million; depreciation and amortization of $3.7 million; a $2.8 million impairment of a long term asset acquired as part of the EQRx Acquisition; amortization of operating lease right-of-use asset of $1.8 million, offset by net amortization of premium on marketable securities of $26.1 million and a $5.8 million change in fair value of warrant liabilities and contingent earn-out shares.

Current wording

During the nine months ended September 30, 2024, cash used in operating activities of $419.1 million was attributable to a net loss of $405.5 million and a net change of $41.6 million in our operating assets and liabilities and $28.0 million in non-cash charges. The change in operating assets and liabilities was primarily due to a $35.8 million decrease in accounts payable; a $4.6 million increase in prepaid expenses and other current assets; a $5.9 million increase in other noncurrent assets; a $1.2 million decrease in operating lease liability offset by a $3.7 million decrease in accrued expenses and other current liabilities; and a $1.3 million decrease in accounts receivable. The non-cash charges primarily consisted of stock-based compensation expense of $56.8 million; depreciation and amortization of $5.6 million; a $2.8 million impairment of a long term asset acquired as part of the EQRx Acquisition; amortization of operating lease right-of-use asset of $2.8 million, offset by net amortization of premium on marketable securities of $35.7 million; and a $4.5 million change in fair value of warrant liabilities and contingent earn-out shares.

Previous wording

During the six months ended June 30, 2023, cash used in operating activities of $129.5 million was attributable to a net loss of $166.4 million offset by $18.6 million in non-cash charges and a net change of $18.3 million in our operating assets and liabilities. The non-cash charges primarily consisted of stock-based compensation expense of $22.7 million; depreciation and amortization of $3.0 million and amortization of operating lease right-of-use asset of $1.3 million, offset by net amortization of premium on marketable securities of $8.4 million. The change in operating assets and liabilities was primarily due to a $7.6 million increase in accounts payable; a $13.4 million increase in accrued expenses and other current liabilities; and a $2.2 million decrease in accounts receivable, offset by a $4.5 million decrease in deferred revenue associated with the Sanofi Agreement.

Current wording

During the nine months ended September 30, 2023, cash used in operating activities of $230.0 million was attributable to a net loss of $274.8 million offset by $29.2 million in non-cash charges and a net change of $15.6 million in our operating assets and liabilities. The non-cash charges primarily consisted of stock-based compensation expense of $36.3 million; depreciation and amortization of $4.5 million and amortization of operating lease right-of-use asset of $2.0 million offset by net amortization of premium on marketable securities of $13.6 million. The change in operating assets and liabilities was primarily due to an $8.2 million increase in accounts payable; a $21.0 million increase in accrued expenses and other current liabilities; a $4.4 million decrease in accounts receivable; a $0.7 million increase in liabilities towards employee stock purchase plan offset by a $0.4 million increase in prepaid expenses and other current assets primarily resulting from the timing of prepayments made for research and development activities and insurance; an $8.5 million increase in other noncurrent assets; a $4.5 million decrease in deferred revenue associated with the Sanofi Agreement; and a $1.4 million decrease in operating lease liability.

Previous wording

During the six months ended June 30, 2024, cash used in investing activities of $140.0 million was comprised of maturities of marketable securities of $942.1 million partially offset by purchases of marketable securities of $1.1 billion and purchases of property and equipment of $5.6 million.

Current wording

During the nine months ended September 30, 2024, cash used in investing activities of $161.5 million was comprised of maturities of marketable securities of $1.3 billion partially offset by purchases of marketable securities of $1.4 billion and purchases of property and equipment of $9.1 million.

Previous wording

During the six months ended June 30, 2023, cash used in investing activities of $39.5 million was comprised of purchases of marketable securities of $369.3 million and purchases of property and equipment of $2.9 million offset by maturities of marketable securities of $332.6 million.

Current wording

During the nine months ended September 30, 2023, cash used in investing activities of $37.8 million was comprised of purchases of marketable securities of $539.3 million and purchases of property and equipment of $5.4 million offset by maturities of marketable securities of $582.5 million.

Previous wording

During the six months ended June 30, 2024, cash provided by financing activities comprised of $5.2 million in proceeds from the issuance of common stock upon the exercise of stock options and $3.2 million in proceeds from the issuance of common stock related to our 2020 Employee Stock Purchase Plan (the ESPP).

Current wording

During the nine months ended September 30, 2024, cash provided by financing activities comprised of $74.3 million in net proceeds from the issuance of common stock under the 2021 ATM and the 2024 ATM; $8.2 million in proceeds from the issuance of common stock upon the exercise of stock options; and $3.2 million in proceeds from the issuance of common stock related to our 2020 Employee Stock Purchase Plan (the ESPP).

Previous wording

During the six months ended June 30, 2023, cash provided by financing activities of $388.8 million was primarily comprised of $323.7 million in net proceeds from issuance of common stock from the March 2023 underwritten public offering; $62.1 million in net proceeds from the issuance of common stock under the ATM and $2.1 million in proceeds from the issuance of common stock related to the ESPP.

Current wording

During the nine months ended September 30, 2023, cash provided by financing activities of $389.8 million was comprised of $323.7 million in net proceeds from issuance of common stock from the March 2023 underwritten public offering; $62.1 million in net proceeds from the issuance of common stock under the 2021 ATM; $2.1 million in proceeds from the issuance of common stock related to the ESPP; and $2.0 million in proceeds from the issuance of common stock upon the exercise of stock options.

Previous wording

For a discussion of our critical accounting estimates, see Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations in our 2023 Form 10-K. There have been no material changes to these critical accounting estimates since our 2023 Form 10-K.

Current wording

For a discussion of our critical accounting estimates, see Part II, Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations in our 2023 Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the SEC on February 26, 2024 (2023 Form 10-K). There have been no material changes to these critical accounting estimates since our 2023 Form 10-K.