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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): November 5, 2021

 

Prelude Therapeutics Incorporated

(Exact Name of Registrant as Specified in its Charter)

 

Delaware		001-39527				81-1384762
(State or other jurisdiction of incorporation or organization)		(Commission File Number)				(I.R.S. Employer Identification No.)
200 Powder Mill Road Wilmington, Delaware				19803
(Address of principal executive offices)				(Zip Code)

Registrant’s telephone number, including area code: (302) 467-1280

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common Stock, $0.0001 par value per share		PRLD		Nasdaq Global Select Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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Item 2.02 Results of Operations and Financial Condition.

On November 12, 2021, Prelude Therapeutics Incorporated (the “Company”) issued a press release announcing its financial results for the three months ended September 30, 2021. A copy of the press release is attached as Exhibit 99.1 to this report.

The information in this Item 2.02, including Exhibit 99.1 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.

Item 5.02 Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers

Departure of Chief Financial Officer

On November 5, 2021, Brian Piper, the Chief Financial Officer of the Company, notified the Company that he will be resigning from the Company, effective November 19, 2021, to pursue other opportunities. On November 5, 2021, the Board of Directors of the Company (the “Board”) appointed Laurent Chardonnet as the Chief Financial Officer of the Company, including as the “principal financial officer” and “principal accounting officer” of the Company within the meaning of Rule 16a-1(f) under the Securities Exchange Act of 1934, as amended, effective on or about November 29, 2021 (the “Appointment Date”).

Before joining the Company, Mr. Chardonnet, age 57, served as Senior Vice President and Chief Financial Officer of Axcella Health Inc. from November 2019 until November 2021. From 2004 to November 2019, Mr. Chardonnet served in various positions at Incyte Corporation, including Vice President, Treasurer and Principal Accounting Officer, Head of Finance and Administration for the Incyte’s European division; and as Vice President of Alliances Prior to Incyte, Mr. Chardonnet served as Controller, Vice President of Finance and acting Chief Financial Officer of Drug Abuse Sciences, a privately held biotechnology company, and as a senior consultant at PricewaterhouseCoopers LLP. Mr. Chardonnet received his Master of Business Administration from Vanderbilt University and his initial business degree from the Institut Superieur de Gestion in Paris.

In connection with Mr. Chardonnet’s appointment as Chief Financial Officer, the Compensation Committee of the Board approved the Company’s entry into an employment agreement (the “Employment Agreement”) with Mr. Chardonnet, which includes the following terms: (i) an initial annual base salary of $400,000 per year (the “Initial Base Salary”), (ii) an annual discretionary bonus of up to 40% of the Initial Base Salary (the “Target Bonus”), (iii) an option to purchase up to 180,000 shares of Company’s common stock (“Common Stock”) (the “Option Award”) with 1/4th of the shares underlying the Option Award vesting and becoming exercisable on the one-year anniversary of the Appointment Date, and 1/48th of the shares underlying the Option Award vesting and becoming exercisable on a monthly basis thereafter, among other benefits. Additionally, in the event Mr. Chardonnet experiences a termination of his employment without “cause” or he resigns for “good reason” (each as defined in the Employment Agreement), provided that he executes and makes effective a release of claims against the Company and its affiliates, Mr. Chardonnet will become entitled to (i) continued base salary for twelve months, payable in accordance with the Company’s standard payroll practices; and (ii) premium payments for continued healthcare coverage for up to nine months. In the event Mr. Chardonnet experiences a termination without “cause” or he resigns for “good reason” during the 12-month period following a change in control, then in lieu of the foregoing, Mr. Chardonnet would become entitled to (a) continued base salary for 12 months, payable in accordance with the Company’s standard payroll practices; (b) 100% of his annual target bonus, payable in a single lump-sum; (c) premium payments for continued healthcare coverage for up to 12 months; and (d) 100% accelerated vesting his then-outstanding equity awards. Mr. Chardonnet will also receive a one-time signing bonus of $160,000 in January 2022.

The foregoing summary of the Employment Agreement does not purport to be complete and is subject to, and qualified in its entirety by, the Employment Agreement, which will be filed as an exhibit to the Company’s Annual Report on Form 10-K for the fiscal year ending December 31, 2021.

The Company expects to enter into its standard form of indemnification agreement for directors and executive officers with Mr. Chardonnet. The form of the indemnification agreement was previously filed by the Company as Exhibit 10.1 to the Company’s Registration Statement on Form S-1 filed with the Securities and Exchange Commission on September 4, 2020 and incorporated by reference herein.

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There are no arrangements or understandings between Mr. Chardonnet and any other persons, pursuant to which he was appointed as Chief Financial Officer, no family relationships among any of the Company’s directors or executive officers and Mr. Chardonnet and he has no direct or indirect material interest in any transaction required to be disclosed pursuant to Item 404(a) of Regulation S-K.

Changes to Executive Compensation

 

On November 5, 2021, the Compensation Committee of the Board of the Company approved a one-time cash bonus (the “Retention Bonus”) to Deborah Morosini, the Company’s Executive Vice President and Chief of Clinical Affairs, in the amount of $200,000 to be paid on November 30, 2022 (the “Award Date”), so long as Dr. Morosini remains employed by the Company on the Award Date.

Item 7.01 Regulation FD Disclosure

The Company has prepared investor presentation materials with information about the Company, which it intends to use as part of investor presentations. A copy of the investor presentation materials to be used by management for presentations is attached as Exhibit 99.2 to this Current Report on Form 8-K and is incorporated herein by reference.

 

The information furnished with this report, including Exhibit 99.2, shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Exchange Act or the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such a filing.

 

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit Number		Description
99.1		Press release issued by Prelude Therapeutics Incorporated regarding its financial results for the three months ended September 30, 2021, dated November 12, 2021.
99.2		Presentation
104		Cover Page Interactive Data File (embedded within the Inline XBRL Document)

 

 

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SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	PRELUDE THERAPEUTICS INCORPORATED
Date: November 12, 2021	By:	/s/ Brian Piper
		Brian Piper
		Chief Financial Officer

 

 

Exhibit 99.1

 

 

Prelude Therapeutics Announces Third Quarter 2021 Financial Results and Operations Update

 

PRT543 and PRT811 Demonstrate Favorable Safety Profile, Tolerability and Evidence of Preliminary Clinical Activity in Phase 1 Dose Escalation in Unselected Patients

 

Phase 1 Dose Expansion Ongoing in Biomarker-Selected Solid Tumor and Hematologic Malignancy Expansion Cohorts for PRT543; Dose Expansion Portion of Phase 1 Trial of PRT811 to Commence 4Q21 with Data Readouts Anticipated for Both Programs in 2022

 

PRT2527 IND Cleared by FDA; Phase 1 Clinical Trial Evaluating IV Monotherapy in Patients with Selected Solid Tumors Anticipated to Begin by Year-End

 

Strong Cash, Cash Equivalents and Marketable Securities Position of $320 Million to Support Clinical and Discovery Pipeline Advancement

 

 

Wilmington, DE – November 12, 2021 – Prelude Therapeutics Inc. (Nasdaq: PRLD), a clinical-stage precision oncology company, today announced its financial results for the third quarter ended September 30, 2021 and provided an update on recent clinical and development pipeline progress.

 

“We continue to make significant progress advancing our novel pipeline of therapeutic candidates, most notably with the recent presentation of dose escalation data from the Phase 1 trials of our lead PRMT5 inhibitors, PRT543 and PRT811,” said Kris Vaddi, PhD, Chief Executive Officer. “We were pleased by these initial data in unselected patients, which demonstrated key points of differentiation for our molecules, including good tolerability and potency, and a desirable therapeutic window. In addition, evidence of preliminary clinical activity was observed in multiple tumor types displaying preclinically validated genomic features. We look forward to leveraging learnings from these data as we execute on the dose escalation portion of the trials and evaluate PRT543 and PRT811 in biomarker-selected patient populations, with data readouts from these cohorts anticipated in 2022. Beyond our PRMT5 inhibitors, the balance of our pipeline continues to advance. During the quarter we received IND clearance from the FDA for PRT2527, our CDK9 inhibitor, positioning us to commence a Phase 1 study of this molecule before year-end.”

 

Recent Highlights and Upcoming Milestones

 

PRT543

 

 

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PRT811

 

 

PRT1419

 

 

PRT2527

 

 

 

Discovery Programs

 

 

Corporate Update

 

 

 

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Third Quarter 2021 Financial Results

 

 

 

 

 

 

 

 

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About Prelude Therapeutics

 

Prelude Therapeutics is a clinical-stage precision oncology company developing innovative, potential best-in-class molecules targeting critical cancer cell pathways involved in cancer pathogenesis. Prelude’s initial clinical candidates, PRT543 and PRT811, are potent, selective, oral PRMT5 inhibitors in Phase 1 development for the treatment of advanced solid tumors, primary and secondary CNS cancers and select myeloid malignancies. PRT1419, a potent and selective MCL1 inhibitor, is in Phase 1 development for patients with relapsed/refractory hematologic malignancies and solid tumors. PRT2527, a highly selective CDK9 inhibitor, is anticipated to begin Phase 1 clinical development by year-end as a monotherapy in patients with selected solid tumors.  In addition, the Company’s pipeline includes PRT-SCA2, a SMARCA2 protein degrader, PRT-K4, a highly selective kinase inhibitor, and additional discovery stage programs.

 

Cautionary Note Regarding Forward-Looking Statements

 

This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, anticipated discovery, preclinical and clinical development activities, timing of availability and announcements of clinical results, the timing of the expansion portion for its Phase 1 clinical trial for PRT543, PRT811 and PRT1419, the timing of IND-related activities for PRT2527 and PRT-SCA2 and the potential benefits of the Company’s product candidates and platform. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. Although the Company believes that the expectations reflected in such forward-looking statements are reasonable, the Company cannot guarantee future events, results, actions, levels of activity, performance or achievements, and the timing and results of biotechnology development and potential regulatory approval is inherently uncertain. Forward-looking statements are subject to risks and uncertainties that may cause the Company’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the Company’s ability to advance its product candidates, the receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, the impact of the COVID-19 pandemic on the Company’s business, clinical trial sites, supply chain and manufacturing facilities, the Company’s ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, the Company’s ability to fund development activities and achieve development goals, the Company’s ability to protect intellectual property, and other risks and uncertainties described under the heading “Risk Factors” in documents the Company files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

 

 

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STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

(UNAUDITED)

 

 

 

 

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BALANCE SHEETS

(UNAUDITED)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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Investor Contacts:
Stacey Jurchison
Executive Director, Corporate Affairs
sjurchison@preludetx.com

 

Melissa Forst
Argot Partners
212.600.1902
prelude@argotpartners.com

 

Media Contact:
Paige Donnelly
Argot Partners
212.600.1902
prelude@argotpartners.com

 

 

 

Corporate Presentation November 2021 Exhibit 99.2

2 Disclaimer This presentation contains “forward-looking” statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: our plans to develop and commercialize small molecule therapies, our expectations about timing and ability to commence, enroll or complete clinical studies and to obtain regulatory approvals for PRT543, PRT811, PRT1419, PRT2527 and other candidates in development, the ability of our product candidates to treat various cancers, the ability to discover additional suitable candidates for regulatory approval, the potential impact of the COVID-19 pandemic and the sufficiency of our cash and cash equivalents to fund our operations. Any statements contained herein or provided orally that are not statements of historical fact may be deemed to be forward-looking statements. In some cases, you can identify forward-looking statements by such terminology as ‘‘believe,’’ ‘‘may,’’ ‘‘will,’’ ‘‘potentially,’’ ‘‘estimate,’’ ‘‘continue,’’ ‘‘anticipate,’’ ‘‘intend,’’ ‘‘could,’’ ‘‘would,’’ ‘‘project,’’ ‘‘plan,’’ ‘‘expect’’ and similar expressions that convey uncertainty of future events or outcomes, although not all forward-looking statements contain these words. Statements, including forward-looking statements, speak only to the date they are provided (unless an earlier date is indicated). These forward-looking statements are based on the beliefs of our management as well as assumptions made by and information currently available to us. Although we believe the expectations reflected in such forward-looking statements are reasonable, we can give no assurance that such expectations will prove to be correct. If such assumptions do not fully materialize or prove incorrect, the events or circumstances referred to in the forward-looking statements may not occur. We undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, except as required by law. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Additional risks and uncertainties that could affect our business are included under the caption “Risk Factors” in our Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission for the three months ended June 30, 2021.

Powered by scientists with a track record of delivering precision oncology medicines Discovery Engine 3 Prelude Therapeutics Vision Efficient development path with potential for rapid regulatory approvals Regulatory Strategy Rapidly advancing potentially high value therapy candidates with a commitment to future patient access, awareness and support Commercial Approach Highly selected patient populations with significant unmet need Clinical Development Patient Focused

Focused Clinical Development Optimized for early clinical POC and rapid execution of pivotal trials CHEMICAL LEADS NOVEL INTERVENTION POINTS Medicinal Chemistry Capabilities Rapidly building synthetically complex molecules  Cancer Biology & Translational Expertise Deep understanding of oncogenic pathways with translational focus METHYLTRANSFERASES KINASES PROTEIN-PROTEIN INTERACTIONS LEVERAGE Our advanced medicinal chemistry capabilities to create better product candidates PURSUE Targets that drive cancers with high unmet need IDENTIFY Target mechanisms with compelling biological rationale 4 Prelude Discovery and Development Approach Target Selection Discovery Engine Pipeline DEGRADERS

5 Prelude Therapeutics Pipeline

6 Prelude Roadmap for Value Creation Anticipated 2021/2022 Milestones Future Strategy PRMT5 Report P1 dose expansion data Generate POC in selected patients Leverage initial POC clinical data to inform design of P2 registration studies MCL1 Complete dose escalation and initiate expansion/combination phase Advance multiple precision oncology clinical programs focusing on underserved cancers CDK9 SMARCA2/ Kinase Initiate Phase 1 clinical trial in selected solid tumors Continue to resource discovery engine to expand our pipeline Complete IND-enabling studies and file INDs Maximize portfolio value through strategic partnerships

PRMT5 Programs

8 PRMT5 Pathway Drives Oncogenesis and Resistance PRMT5 Transcription Factors PRMT5 Spliceosome Histones Transcriptional Control of Oncogenesis and Resistance DNA Repair Genes HRD+ Cancers (e.g., Ovarian, Breast) Oncogenic Drivers (e.g., Myc / Myb) ACC, Lymphomas, Richter’s Splicing Dysregulation / Mutations Myeloid Malignancies, GBM, Uveal Melanoma, NSCLC sDMA

9 Prelude PRMT5 Program Optimized for a well-balanced and differentiated profile Differentiating Mechanism of Action Prelude compounds are co-factor (SAM) competitive inhibitors Substrate competitive Inhibitors PRMT5

10 PRT543 / PRT811 Differentiated Clinical Stage Oral PRMT5 Inhibitors PRT543 PRT811 Strong scientific rationale for pathway Highly selective and potent oral candidate Optimized PK profile Good oral bioavailability and long half-life (12+ hours) Applicability in both solid tumors and heme malignancies Completed dose escalation; Currently in expansion phase in selected patient cohorts Brain-penetrant PRMT5 inhibitor High/sustained brain exposure in preclinical studies Optimized PK profile 5+ hours half-life; maximizing therapeutic window Highly selective and potent oral candidate Completed Dose escalation; Expansion phase to begin

PRT543 /PRT811 Phase 1 Dose Escalation Data

12 Study Demographics & Safety 49 patients Unselected patient population with 18 different diagnoses 9 colon; 7 ACC; 6 uveal melanoma (2 patients SF3B1+); 5 ovarian cancer (2 patients HRD+) Median of 3 prior lines of systemic therapy PRT543 was well-tolerated Most common TRAEs of any grade in ≥ 5% of all patients: fatigue, thrombocytopenia, anemia, nausea The most common Grade 3≥ AEs were thrombocytopenia and anemia Reversible upon dose modification Thrombocytopenia was only dose-limiting toxicity No discontinuations due to toxicity Preliminary Clinical Activity Stable disease for at least 6 months and tumor regressions (<30%) in 5 patients including ACC and uveal melanoma Durable CR in a patient with HRD+ ovarian cancer Multiple lines of prior therapy, including PARPi One target lesion per RECIST and CA125 level 37.8 U/mL at baseline RECIST v1.1 CR at first follow-up tumor assessment (7 weeks), maintained throughout the study CA125 reduced and remained below 5 U/mL at the last assessment Patient remains on study following 18 months of treatment at 35 mg 5x/week *Data as of August 6, 2021 Data presented at 2021 AACR-NCI-EORTC Annual Meeting PRT543: Well-Tolerated with Evidence of Preliminary Clinical Activity in Phase 1 Dose Escalation Study* 02/12/2020 (Baseline) 10/14/2020

13 PRT543: Exhibited Target Engagement and Inhibited PRMT5 Activity in Phase 1 Dose Escalation Study Dose-Dependent Increases in Cmax and AUC Dose-Dependent Inhibition of Serum sDMA Intron Retention Observed at Higher Dose Levels 45 mg/5x week selected as recommended Phase 2 dose Data presented at 2021 AACR-NCI-EORTC Annual Meeting

14 PRT543 – Timeline and Clinical Plan Myeloid Malignancies with Spliceosome Mutations (N~20) Myelofibrosis PRT543 + Ruxolitinib (N~20) Myelofibrosis/MDS Monotherapy (N~40) Dose escalation completed Expansion dose and schedule confirmed Dose expansion cohorts enrolling Dose expansion data readouts anticipated in 2022 Demonstrate initial proof of concept Design Phase 2/3 studies based on POC data from the expansion cohorts Commence Phase 2/3 registration studies 2022 2021

15 PRT811: Well-Tolerated with Evidence of Preliminary Clinical Activity in Phase 1 Dose Escalation Study *Data as of August 13, 2021 **Data as of September 20, 2021 Data presented at 2021 AACR-NCI-EORTC Annual Meeting 45 patients 27 across 16 unselected advanced solid tumors 18 patients with high-grade glioma: 17 relapsed/refractory GBM and 1 anaplastic astrocytoma 1/17 patients with IDH1 mutated GBM PRT811 was well tolerated Most common TRAEs of any grade in ≥ 5% of all patients: nausea, vomiting, fatigue, thrombocytopenia Grade 3 ≥ AEs were uncommon occurring in 11% of patients No DLTs at doses up to 600 mg QD Two SF3B1+ uveal melanoma patients demonstrated anti tumor activity – both patients continuing on treatment One patient had an uPR (47% decrease in target lesion) and continuing on therapy** One patient had SD (25% decrease in target lesion for >6 months and continuing on therapy* One patient with triple negative breast cancer had a 27% decrease in target lesions** One patient with IDH1 mutated GBM experienced durable PR that evolved into CR* Baseline: one target lesion per RANO Prior treatment: surgery and chemoradiation + temozolomide Nov/20: 77% reduction of target lesion, confirmed PR; August 2021: confirmed CR Study Demographics & Safety Preliminary Clinical Activity

16 PRT811: Exhibited Target Engagement and Inhibited PRMT5 Activity in Phase 1 Dose Escalation Study Dose-Dependent Increases in Cmax and AUC Dose-dependent Inhibition of Serum sDMA Intron Retention Observed at Higher Dose Levels Data presented at 2021 AACR-NCI-EORTC Annual Meeting

17 PRT543 and PRT811: Overall Response and Response Duration in Select Patient Cohorts From Dose Escalation Phase †Target lesions assessed using RECIST, except for patient 811-F with glioma assessed by RANO. ‡Data cutoff for PRT543 was 8.6.21, for PRT811 was 8.13.21, and for patient 811-E was 10.8.21. ACC, adenoid cystic carcinoma; CR, complete response; HRD, homologous recombination deficiency; IDH, isocitrate dehydrogenase; PD, progressive disease; PR, partial response; PRMT, protein arginine methyltransferase; RANO, Response Assessment in Neuro-Oncology; RECIST, Response Evaluation Criteria In Solid Tumors; SD, stable disease; SPLC, splicing mutation. Overall Response and Duration 0 28 56 84 112 140 168 196 224 252 280 308 336 364 392 420 448 476 504 532 560 588 Time on Treatment (days) † ‡ CR PR CR PR 811-G 811-A 543-B 543-L 811-C 543-E 543-J 543-F 543-G 543-I 811-B 543-H 543-A 543-K 811-F 811-H 543-C 811-E 543-D 811-D

18 PRT543 and PRT811: Overall Response of Target Lesions (RECIST or RANO) in Select Patient Cohorts From Dose Escalation Phase *Data cutoff for PRT543 was 8.6.21, for PRT811 was 8.13.21, and for patient 811-E was 10.8.21. †Target lesions assessed using RECIST, except for patient 811-F with glioma assessed by RANO. ACC, adenoid cystic carcinoma; CR, complete response; HRD, homologous recombination deficiency; IDH, isocitrate dehydrogenase; PD, progressive disease; PR, partial response; PRMT, protein arginine methyltransferase; RANO, Response Assessment in Neuro-Oncology; RECIST, Response Evaluation Criteria In Solid Tumors; SD, stable disease; SPLC, splicing mutation.

19 PRT811 – Timeline and Clinical Plan Dose escalation completed Dose expansion cohorts to begin enrolling Dose expansion data readouts anticipated in 2022 Demonstrate initial clinical proof of concept Design Phase 2/3 studies based on POC data from expansion cohorts Commence Phase 2/3 registration studies 2022 2021 HRD+ tumors (brain metastatic) (N~20) Primary CNS Lymphoma (N~20) IDHm high-grade gliomas (N~20) Uveal melanoma (N~20)

MCL1 Program

21 Prelude MCL1 Program Dysregulated MCL1 expression occurs frequently in cancer MCL1 is a member of BCL2 family of proteins involved in blocking cell death proteins MCL1 is a validated bypass and resistance mechanism for venetoclax (BCL2 inhibitor) and TKIs Currently active competitor compounds are IV candidates Challenging medicinal chemistry target that requires disruption of protein-protein interaction Significant opportunity in post-venetoclax setting MCL1

PRT1419 Differentiated Clinical-Stage MCL1 Inhibitor Candidate 22 MCL1 22

23 PRT1419: Potential Leading MCL1 Inhibitor Prelude compounds are competitive inhibitors of BIM binding Highly Potent Binding to MCL1 MCL1

24 PRT1419 Demonstrated Preclinical Activity as Monotherapy and in Combination Monotherapy Combination MCL1

Dose Escalation Expansion Cohorts 25 Oral PRT1419 Phase 1 Clinical Trial CURRENT MCL1 Group A Group B 100mg 1x/wk 200mg 1x/wk 100mg 1x/wk AML (N~20) AML or MDS PRT1419 + Venetoclax or Aza (N~20) NHL (B or T cell Lymphoma) (N~20) Multiple Myeloma (N~20) High Risk MDS (N~20) Recommended Expansion Dose Recommended Expansion Dose Status as of December 16, 2020

CDK9 Program PRT2527

27 Prelude CDK9 Program CDK9 phosphorylates RNA Pol II and regulates transcription Regulates expression of several immediate early genes driving oncogenesis and resistance (i.e. MYC, MYB, MCL1) Non-selective CDK9 inhibitors have demonstrated clinical activity in multiple tumor types but poor tolerability Lack of selectivity and potency vs other CDK9s is believed to contribute to low therapeutic window CDK9

28 PRT2527: Potent and Highly Selective CDK9 Inhibitor Candidate Highly Selective CDK9 Inhibitor Candidate CDK9 Prelude compounds are ATP competitive inhibitors *Internal data; biochemical assay at 1 mM ATP, H929 CTG proliferation assay; **VIP151 was formerly BAY151and licensed to Vincera by Bayer

29 CDK9 Inhibitor Candidate: PRT2527 Improved Selectivity Sustained Regressions at Well-Tolerated Doses in Vivo Potent in Vitro Activity CDK9

SMARCA2 Program

31 SMARCA2 Targeted Degrader Program SMARCA4 and SMARCA2 Regulate Chromatin Accessibility and Gene Expression Loss of SMARCA4 Leads to SMARCA2 Dependency SMARCA2 SMARCA4 MUTANT TUMORS SMARCA2 Degradation Dysfunctional SMARCA4 Synthetic Lethality Tumor Cell Death SMARCA4

32 PRT-SCA2: Potent Selective SMARCA2 Degraders with In Vivo Activity SMARCA2 Prelude SMARCA2 Degraders Replicate Genetic Synthetic Lethality Sub-Nanomolar Potency for SMARCA2 Degradation Highly Selective for SMARCA2 Degradation %inhibition %Conc(nM) In vitro In vivo

Corporate Highlights

Financial Summary Shares Outstanding 47.0 million shares voting and non-voting common stock as of Nov 8, 2021 61.0 million shares fully diluted 34 Cash, Cash Equivalents and Marketable securities $320.9 million as of Sept 30, 2021 The Company believes that its current cash, cash equivalents and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into the second half of 2023

35 Prelude Roadmap for Value Creation Anticipated 2021/2022 Milestones Future Strategy PRMT5 Report P1 dose expansion data Generate POC in selected patients Leverage initial POC clinical data to inform design of P2 registration studies MCL1 Complete dose escalation and initiate expansion/combination phase Advance multiple precision oncology clinical programs focusing on underserved cancers CDK9 SMARCA2/ Kinase Initiate Phase 1 clinical trial in selected solid tumors Continue to resource discovery engine to expand our pipeline Complete IND-enabling studies and file INDs Maximize portfolio value through strategic partnerships

Thank You