Prelude Therapeutics Inc

Previous wording

PRT3789 is a first-in-class, highly selective degrader of SMARCA2 protein, which along with SMARCA4 controls gene regulation through chromatin remodeling. Cancer cells with SMARCA4 mutations are dependent on SMARCA2 for their growth and survival and selectively degrading SMARCA2 induces cell death in cancer cells while sparing normal cells in preclinical models. PRT3789 has been shown to be efficacious and well tolerated in multiple preclinical models of SMARCA4 deleted/mutated cancers as monotherapy and in combination with standards of care therapies. We believe a selective SMARCA2 degrader has the potential to be of benefit in up to 10% of non-small cell lung cancer, or NSCLC, patients in the United States including many other tumor types with the SMARCA4 mutation.

Current wording

PRT3789 is a first-in-class, highly selective degrader of SMARCA2 protein, which along with SMARCA4 controls gene regulation through chromatin remodeling. Patients with SMARCA4 mutated cancer have a poor clinical prognosis. We believe this represents an area of high unmet medical need. Cancer cells with SMARCA4 mutations are dependent on SMARCA2 for their growth and survival and selectively degrading SMARCA2 induces cell death in cancer cells while sparing normal cells in preclinical models. We believe a selective SMARCA2 degrader has the potential to be of benefit in up to 10% of non-small cell lung cancer, or NSCLC, patients in the United States including many other tumor types with the SMARCA4 mutation.

Previous wording

PRT3789 is in Phase 1 clinical development in patients with biomarker selected SMARCA4-mutated cancers. We have completed enrollment of monotherapy dose escalation at the 665 mg once weekly IV dose and have selected 500 mg once weekly as the recommended Phase 2 dose. In addition, we have completed dose escalation in the combination of PRT3789 with docetaxel and we are nearing completion of backfill cohorts. Updated data from the trial is expected to be presented at a major medical meeting in the second half of 2025.

Current wording

PRT3789 has completed Phase 1 clinical development in patients with biomarker selected SMARCA4-mutated cancers. The Company anticipates providing updated data from the Phase 1 study by year-end 2025.

Previous wording

Our discovery team has identified a series of potent, selective and orally bioavailable SMARCA2 degraders. In July 2024, we received IND clearance for the lead oral molecule, PRT7732. PRT7732 is >1000-fold selective for SMARCA2 vs. SMARCA4 and demonstrates robust activity in SMARCA4 deficient cancer models both as monotherapy and in combination with docetaxel at well-tolerated doses. PRT7732 demonstrates good oral bioavailability and half-life suitable for once daily oral dosing. In the fourth quarter of 2024, the we initiated and enrolled the first patients in a phase 1 multi-dose escalation trial of PRT7732 (NCT06560645) in biomarker selected SMARCA4 mutated cancers. Enrollment has advanced rapidly and we are currently enrolling patients in the fifth dose escalation cohort (60 mg once daily). We expect to provide an initial first-in-human data update at a major medical meeting in the second half of 2025.

Current wording

Our discovery team has identified a series of potent, selective and orally bioavailable SMARCA2 degraders. In July 2024, we received IND clearance for the lead oral molecule, PRT7732. PRT7732 is >1000-fold selective for SMARCA2 vs. SMARCA4 and demonstrates robust activity in SMARCA4 deficient cancer models both as monotherapy and in combination with docetaxel at well-tolerated doses. PRT7732 demonstrates good oral bioavailability and half-life suitable for once daily oral dosing. In the fourth quarter of 2024, the we initiated and enrolled the first patients in a phase 1 multi-dose escalation trial of PRT7732 (NCT06560645) in biomarker selected SMARCA4 mutated cancers. Enrollment continues to advance rapidly, and we are currently enrolling patients in the seventh dose escalation cohort (125 mg once daily). We expect to provide an initial first-in-human data update including PK/PD, safety and initial clinical activity at biologically relevant doses by year-end 2025.

Previous wording

We have discovered and are developing a series of selective and orally bioavailable KAT6A degraders. Optimized lead compounds are advancing to candidate nomination in the second quarter of 2025 with intent to file an IND in 2026. KAT6 is a clinically validated target with promising activity in breast cancer and other solid tumors. We recently presented preclinical data from this program at the American Association for Cancer Research (AACR) 2025 Annual Meeting. We intend to develop this program to IND and are open to development with a partner.

Current wording

We have discovered and are developing a series of selective and orally bioavailable KAT6A selective degraders. We are now advancing a development candidate and remain on track to file an IND in the first half of 2026. KAT6 is a clinically validated target with promising activity in breast cancer and other solid tumors. We recently presented preclinical data from this program at the American Association for Cancer Research (AACR) 2025 Annual Meeting.

Previous wording

Our CDK9 candidate, PRT2527, is a potent and highly selective CDK9 inhibitor that has the potential to avoid off-target toxicities observed with other less selective CDK9 inhibitors. We presented interim phase 1 results of the dose-escalation study as part of a poster session at the 66th American Society of Hematology Annual Meeting (ASH) in the fourth quarter of 2024. PRT2527 demonstrated activity across a range of relapsed/refractory lymphoid malignancies, including patients who received prior CAR-T therapy. We also announced that we intend to seek a partner for any future continued advancement of PRT2527, as a result of our strategic focus on the SMARCA2 degrader development program.

Current wording

Our CDK9 candidate, PRT2527, is a potent and highly selective CDK9 inhibitor that has the potential to avoid off-target toxicities observed with other less selective CDK9 inhibitors. We presented interim phase 1 results of the dose-escalation study as part of a poster session at the 66th American Society of Hematology Annual Meeting (ASH) in the fourth quarter of 2024. PRT2527 demonstrated activity across a range of relapsed/refractory lymphoid malignancies, including patients who received prior CAR-T therapy. As previously announced, we intend to seek a partner for any future continued advancement of PRT2527.

Previous wording

Since inception, we have devoted substantially all of our resources to developing product and technology rights, conducting research and development, organizing and staffing our company, business planning and raising capital. We have incurred recurring losses, the majority of which are attributable to research and development activities, and negative cash flows from operations. We have funded our operations primarily through the sale of convertible preferred stock, common stock and pre-funded warrants. Our net loss was $32.1 million and $31.4 million for the three months ended March 31, 2025 and 2024, respectively. As of March 31, 2025, we had an accumulated deficit of $615.6 million. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative expenditures. Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current or future product candidates. We expect to continue to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through all stages of development and clinical trials and, ultimately, seek regulatory approval. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials and our expenditures on other research and development activities.

Current wording

Since inception, we have devoted substantially all of our resources to developing product and technology rights, conducting research and development, organizing and staffing our company, business planning and raising capital. We have incurred recurring losses, the majority of which are attributable to research and development activities, and negative cash flows from operations. We have funded our operations primarily through the sale of convertible preferred stock, common stock and pre-funded warrants. Our net loss was $63.3 million and $66.2 million for the six months ended June 30, 2025 and 2024, respectively. As of June 30, 2025, we had an accumulated deficit of $646.9 million. Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative expenditures. Our ability to generate product revenue sufficient to achieve profitability will depend heavily on the successful development and eventual commercialization of one or more of our current or future product candidates. We expect to continue to incur significant expenses and operating losses for the foreseeable future as we advance our product candidates through all stages of development and clinical trials and, ultimately, seek regulatory approval. In addition, if we obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year, depending on the timing of our clinical trials and our expenditures on other research and development activities.

Previous wording

Research and development expenses increased from $27.4 million for the three months ended March 31, 2024 to $28.8 million for the three months ended March 31, 2025. Included in research and development expenses for the three months ended March 31, 2025, was $2.3 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $3.0 million for the three months ended March 31, 2024. Research and development expenses increased primarily due to an increase in expense related to our SMARCA2 clinical trials. Research and development expenses may fluctuate from period to period depending upon the stage of certain projects and the level of preclinical and clinical trial-related activities.

Current wording

Research and development expenses decreased from $29.5 million for the three months ended June 30, 2024 to $25.8 million for the three months ended June 30, 2025. Included in research and development expenses for the three months ended June 30, 2025, was $2.2 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $3.4 million for the three months ended June 30, 2024. Along with the decrease in stock-based compensation expense, research and development expenses decreased due to a decrease in expense related to our SMARCA2 clinical trials. Research and development expenses may fluctuate from period to period depending upon the stage of certain projects and the level of preclinical and clinical trial-related activities.

Previous wording

General and administrative expenses decreased from $6.9 million for the three months ended March 31, 2024 to $5.8 million for the three months ended March 31, 2025. The decrease was primarily driven by a decrease in non-cash expense related to stock-based compensation expense. Included in general and administrative expenses for the three months ended March 31, 2025, was $1.6 million of non-cash expense related to stock-based compensation expense compared to $2.5 million for the three months ended March 31, 2024, due to the tapering off of the vesting period of prior granted options and lower valuation on more recent grants due to the decrease in our stock price.

Current wording

General and administrative expenses decreased from $7.7 million for the three months ended June 30, 2024 to $6.4 million for the three months ended June 30, 2025. The decrease was primarily driven by a decrease in non-cash expense related to stock-based compensation expense. Included in general and administrative expenses for the three months ended June 30, 2025, was $1.6 million of non-cash expense related to stock-based compensation expense compared to $2.7 million for the three months ended June 30, 2024, due to the tapering off of the vesting period of prior granted options and lower valuation on more recent grants due to the decrease in our stock price.

Previous wording

Other income, net decreased from $2.9 million for the three months ended March 31, 2024, to $2.5 million for the three months ended March 31, 2025 primarily due to lower income earned our investments due to lower balances offset by the receipt and recognition of research and development tax credits.

Current wording

Other income, net decreased from $5.3 million for the six months ended June 30, 2024, to $3.5 million for the six months ended June 30, 2025 primarily due to lower income earned our investments due to lower balances partially offset by the receipt and recognition of research and development tax credits.

Previous wording

At March 31, 2025 the Company had cash, cash equivalents, restricted cash and marketable securities totaling $103.1 million. Absent additional funding, the Company believes that its cash, cash equivalents, restricted cash and marketable securities will not be sufficient fund its operating expenses and capital expenditure requirements for at least the next twelve months from the filing date of this Quarterly Report on Form 10-Q. As a result, substantial doubt exists about our ability to continue as a going concern.

Current wording

At June 30, 2025 the Company had cash, cash equivalents, restricted cash and marketable securities totaling $77.3 million. Absent additional funding, the Company believes that its cash, cash equivalents, restricted cash and marketable securities will not be sufficient to fund its operating expenses and capital expenditure requirements for at least the next twelve months from the filing date of this Quarterly Report on Form 10-Q. As a result, substantial doubt exists about our ability to continue as a going concern.

Previous wording

During the three months ended March 31, 2025, we used $34.2 million of cash in operating activities. Cash used in operating activities reflected our net loss of $32.1 million and a $6.9 million net increase in our operating assets and liabilities offset by noncash charges of $4.7 million, which primarily consisted of stock-based compensation. The primary use of cash was to fund our operations related to the development of our product candidates.

Current wording

During the six months ended June 30, 2025, we used $60.3 million of cash in operating activities. Cash used in operating activities reflected our net loss of $63.3 million and a $6.1 million net increase in our operating assets and liabilities offset by noncash charges of $9.1 million, which primarily consisted of stock-based compensation. The primary use of cash was to fund our operations related to the development of our product candidates.

Previous wording

During the three months ended March 31, 2024, we used $31.8 million of cash in operating activities. Cash used in operating activities reflected our net loss of $31.4 million and a $5.2 million net increase in our operating assets and liabilities, offset by noncash charges of $4.8 million, which primarily consisted of stock-based compensation. The primary use of cash was to fund our operations related to the development of our product candidates.

Current wording

During the six months ended June 30, 2024, we used $54.8 million of cash in operating activities. Cash used in operating activities reflected our net loss of $66.2 million offset by noncash charges of $10.5 million, which primarily consisted of stock-based compensation, and $0.9 million net decrease in our operating assets and liabilities. The primary use of cash was to fund our operations related to the development of our product candidates.

Previous wording

During the three months ended March 31, 2025, net cash provided by investing activities of $62.2 million consisted primarily of $71.7 million in proceeds from maturities of marketable securities, partially offset by $9.5 million in purchases of marketable securities. During the three months ended March 31, 2024, net cash used in investing activities of $31.2 million consisted primarily of $37.0 million in proceeds from maturities of marketable securities, partially offset by $5.5 million in purchases of marketable securities.

Current wording

During the six months ended June 30, 2025, net cash provided by investing activities of $73.7 million consisted primarily of $107.9 million in proceeds from maturities of marketable securities, partially offset by $34.1 million in purchases of marketable securities. During the six months ended June 30, 2024, net cash used in investing activities of $57.3 million consisted primarily of $71.4 million in proceeds from maturities of marketable securities, partially offset by $13.4 million in purchases of marketable securities.

Previous wording

For the three months ended March 31, 2025 net cash used in financing activities was primarily for principal payments on our finance lease.

Current wording

For the six months ended June 30, 2025 net cash used in financing activities was primarily for principal payments on our finance lease. For the six months ended June 30, 2024 net cash provided by financing activities was primarily from proceeds received from the issuance of common stock under the employee stock purchase plan, offset by principal payments on our finance lease and the payment of offering costs related to the shelf registration statement.

Previous wording

Subject to certain conditions, as an emerging growth company, we may rely on certain other exemptions and reduced reporting requirements, including without limitation, exemption to the requirements for providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act. We will remain an emerging growth company until the earlier to occur of (a) the last day of the fiscal year (i) following the fifth anniversary of the completion of our initial public offering (i.e. December 31, 2025), (ii) in which we have total annual gross revenues of at least $1.235 billion or (iii) in which we are deemed to be a “large accelerated filer” under the rules of the SEC, which means the market value of our common stock that is held by non-affiliates exceeds $700.0 million as of the prior June 30th, or (b) the date on which we have issued more than $1.0 billion in non-convertible debt during the prior three-year period.

Current wording

Subject to certain conditions, as an emerging growth company, we may rely on certain other exemptions and reduced reporting requirements, including without limitation, exemption to the requirements for providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to Section 404(b) of the Sarbanes-Oxley Act. We anticipate that we will no longer be an emerging growth company as of December 31, 2025 and, as a result, we will no longer be able to take advantage of reduced disclosure and other obligations that are available to emerging growth companies after that date.