Prelude Therapeutics (NASDAQ: PRLD) trims Q1 2026 loss and extends cash runway to 2028
Rhea-AI Filing Summary
Prelude Therapeutics filed an 8-K reporting first quarter 2026 results and a broad R&D update. Revenue reached $4.58 million for the three months ended March 31, 2026, compared with none in the prior-year period, while net loss narrowed to $10.4 million, or $0.13 per share, from $32.1 million, or $0.42 per share.
Research and development expense fell to $13.6 million from $28.8 million, largely due to pausing SMARCA2 trials, and general and administrative expense declined to $5.2 million. Cash, cash equivalents, restricted cash and marketable securities totaled $84.8 million as of March 31, 2026, and an underwritten offering afterward added about $90 million, supporting a projected cash runway into the second quarter of 2028. Operationally, Prelude began enrolling a Phase 1 study of JAK2V617F inhibitor PRT12396 in polycythemia vera and myelofibrosis, plans an IND filing by mid-2026 and Phase 1 start in the second half of 2026 for KAT6A degrader PRT13722, continues discovery work on mCALR-directed degrader antibody conjugates, and appointed Charles Morris, M.D. as Chief Medical Officer.
Positive
- Substantially improved quarterly loss profile: Q1 2026 net loss narrowed to $10.4 million ( $0.13 per share) from $32.1 million ( $0.42 per share) a year earlier, driven by lower R&D and G&A expenses while beginning to generate $4.58 million of revenue.
- Extended cash runway with added capital: Cash, cash equivalents, restricted cash and marketable securities of $84.8 million at March 31, 2026 plus an approximately $90 million underwritten offering support management’s expectation that funding will last into the second quarter of 2028, reducing near-term financing pressure.
- Multiple advancing precision-oncology programs: The company initiated a Phase 1 study of JAK2V617F inhibitor PRT12396 in myeloproliferative neoplasms and plans an IND by mid-2026 with Phase 1 start in the second half of 2026 for KAT6A degrader PRT13722, adding potential future value drivers.
Negative
- None.
Insights
Prelude trimmed losses, extended cash runway, and advanced multiple precision-oncology programs.
Prelude Therapeutics reported Q1 2026 revenue of $4.58 million versus none a year earlier, mainly alongside sharply lower operating expenses. Net loss improved to $10.4 million from $32.1 million, helped by R&D falling to $13.6 million from $28.8 million after pausing SMARCA2 trials.
Cash, cash equivalents, restricted cash and marketable securities were $84.8 million on March 31, 2026, and a subsequent underwritten offering raised about $90 million. Management now expects this liquidity to fund operations into the second quarter of 2028, which is a longer visibility window than many early-stage peers.
Strategically, the company is enrolling a Phase 1 trial of JAK2V617F inhibitor PRT12396 in myeloproliferative neoplasms and targets an IND by mid-2026 plus a second-half Phase 1 start for KAT6A degrader PRT13722 in ER+ breast cancer. Additional work on mCALR-directed degrader antibody conjugates and licensed degrader payloads, together with the appointment of a new Chief Medical Officer, positions the pipeline for multiple clinical catalysts, though outcomes and timelines remain subject to typical development and regulatory risks.
8-K Event Classification
Key Figures
Key Terms
myeloproliferative neoplasms medical
degrader antibody conjugates medical
mutant allele burden medical
Investigational New Drug (IND) regulatory
Phase 1 study medical
non-voting common stock financial
Earnings Snapshot
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d)
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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:
Securities registered pursuant to Section 12(b) of the Act:
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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. ☐
Item 2.02 Results of Operations and Financial Condition.
On May 12, 2026, Prelude Therapeutics Incorporated (the "Company") issued a press release announcing its financial results for the three months ended March 31, 2026. A copy of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K.
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 in this Current Report on Form 8-K and in Exhibits 99.1 and 99.2 attached hereto is being furnished, but shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (“Exchange Act”), and is not incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
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Description |
99.1 |
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Press Release dated May 12, 2026 |
99.2 |
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Presentation |
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Cover Page Interactive Data File (embedded within the Inline XBRL Document) |
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.
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PRELUDE THERAPEUTICS INCORPORATED
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Date: May 12, 2026 |
By: |
/s/ Bryant Lim |
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Bryant Lim |
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Chief Financial Officer and Chief Legal Officer |
Exhibit 99.1
Prelude Therapeutics Reports First Quarter 2026 Financial Results and Provides Corporate Update
Initiated enrollment of Phase 1 Study of PRT12396, mutant-selective JAK2V617F inhibitor in patients with polycythemia vera (PV) and myelofibrosis (MF)
The Company expects to file the IND for PRT13722, first-in-class highly-selective oral KAT6A degrader, by mid-2026 with Phase 1 study initiation in ER+ breast cancer anticipated in the 2H 2026
Presented preclinical data demonstrating differentiated profile of PRT13722, at the American Association for Cancer Research (AACR) Annual Meeting 2026
Appointed Charles Morris, M.D. as Chief Medical Officer
Current cash runway expected into second quarter of 2028 based on preliminary estimates, driven by previously announced underwritten offering with gross proceeds of $90 million
WILMINGTON, Del., May 12, 2026 (GLOBE NEWSWIRE) – Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, today reported its financial results for the first quarter ended March 31, 2026 and provided an update on its R&D pipeline and other corporate developments.
“Through this first quarter of 2026, our company has continued to demonstrate focused execution of the strategic priorities we set forth late last year.” stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. “Since the beginning of this year, we’ve advanced PRT12396 into first-in-human studies, presented promising preclinical data from our highly selective KAT6A degrader development candidate, continued to progress towards a development candidate from our mCALR program and importantly, extended our cash runway into the second quarter of 2028.”
Program Updates and Upcoming Milestones
Mutant selective JAK2V617F JH2 inhibitor program
JAK2V617F is the primary driver mutation responsible for disease progression in the majority of patients living with myeloproliferative neoplasms (MPNs). The mutation impacts approximately 95% of patients with polycythemia vera (PV), 60% of patients with essential thrombocythemia (ET) and 55% of patients with myelofibrosis (MF). Identifying JAK2 JH2 inhibitors that selectively target V617F+ cells has long been the goal for advancing the treatment of MPNs.
Exhibit 99.1
Prelude has designed and identified novel allosteric inhibitors that bind into the JAK2 JH2 “deep pocket” where the V617F mutation resides. These candidates demonstrate mutant specific inhibition in multiple preclinical models of MPNs. Prelude believes this approach may have the potential to reduce mutant allele burden, slow or even reverse disease progression, and transform treatment outcomes for MPN patients.
PRT12396, Prelude’s lead, mutant-selective JAK2V617F inhibitor received IND clearance from the U.S. Food and Drug Administration, as previously announced in February 2026 and recently initiated and commenced enrollment into a Phase 1 study of PRT12396 in patients with PV and MF.
The JAK2V617F inhibitor program is subject to an exclusive option agreement with Incyte announced in November 2025.
Highly selective KAT6A oral degrader program
KAT6 is an emerging and recently validated target in the treatment of ER+ breast cancer. Prelude discovered and is developing first-in-class, highly potent, highly selective and orally bioavailable KAT6A selective degraders. The Company has selected a development candidate, PRT13722 and remains on track to file an IND application in mid-2026, and pending clearance, phase 1 study initiation expected in the 2nd half of 2026. Prelude believes that selectively degrading KAT6A has the potential for improved efficacy, tolerability and combinability with other agents relative to non-selective inhibitors of KAT6A/B.
The Company presented preclinical data supporting this hypothesis at the AACR Annual Meeting 2026. The presentation can be found at Publications - Prelude Therapeutics.
Degrader payloads for next generation DACs
Prelude is leveraging our expertise in targeted protein degradation to discover and develop novel degrader payloads for use with next generation DACs. We have developed highly potent SMARCA2/4 and CDK9 degrader payloads optimized for efficacy, tolerability and developability when coupled to a wide range of different antibodies. Building on our existing DAC partnership with AbCellera, the Company’s payloads and corresponding payload-linkers are available for licensing to additional partners to expand the reach of this new technology.
We have recently published preclinical data demonstrating that next generation DACs using Prelude degrader payloads have potential for significantly better in vivo efficacy and tolerability compared to traditional cytotoxic ADCs when tested head-to-head in xenograft models. These data can be found at: Publications – Prelude Therapeutics
Mutated calreticulin (mCALR) DAC discovery program
Mutant CALR is a neoantigen presented on the cell surface of malignant myeloid cells but not normal cells and is found in approximately 25-35% of patients with MF and essential thrombocythemia (ET). Recently, a mCALR-targeted monoclonal antibody demonstrated robust clinical activity in high-risk ET patients. Prelude is exploring mCALR-targeted DACs using the Company’s proprietary degrader payloads as a differentiated approach for patients with CALR mutations. This early discovery program is wholly owned and controlled by Prelude.
Exhibit 99.1
The Company presented the preclinical data from the program at the European Hematology Association 2025 Congress in June and the American Society of Hematology (ASH) 67th Annual Meeting in December 2025. The presentations can be found at Publications – Prelude Therapeutics.
Corporate Updates
In April 2026, the Company announced the appointment of Charles Morris, M.D. as Chief Medical Officer.
Upcoming Investor Conferences
The Company will participate in the 2026 Jefferies Global Healthcare Conference taking place in New York City. On Wednesday, June 3, 2026 at 12:15 PM ET, Kris Vaddi, Ph.D., Chief Executive Officer, Peggy Scherle, Ph.D., Chief Scientific Officer and Bryant Lim, Chief Financial Officer will participate in a fireside chat.
The Company will also participate in the Goldman Sachs 47th Annual Global Healthcare Conference taking place in Miami, FL. On Wednesday, June 10, 2026 at 11:20 AM ET, Kris Vaddi, Ph.D., Chief Executive Officer, Peggy Scherle, Ph.D., Chief Scientific Officer and Bryant Lim, Chief Financial Officer will participate in a fireside chat.
First Quarter 2026 Financial Results
Cash, Cash Equivalents, Restricted cash and Marketable securities:
Cash, cash equivalents, restricted cash and marketable securities as of March 31, 2026 were $84.8 million. Subsequent to March 31, 2026, the Company completed an underwritten offering with gross proceeds of approximately $90 million. Based on preliminary estimates, the Company anticipates that its existing cash, cash equivalents, restricted cash and marketable securities will fund Prelude’s operations into the second quarter of 2028.
Research and Development (R&D) Expenses:
For the three months ended March 31, 2026, R&D expense decreased to $13.6 from $28.8 million for the prior year period. Included in the R&D expense for the three months ended March 31, 2026 was $1.1 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $2.3 million for the three months ended March 31, 2025. Along with the decrease in stock-based compensation expense, the decrease was primarily related to lower expense incurred for our SMARCA2 clinical trials which we paused in 2025. 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.
General and Administrative (G&A) Expenses:
For the three months ended March 31, 2026, G&A expenses decreased to $5.2 million from $5.8 million for the prior year period. Included in general and administrative expenses for the three
Exhibit 99.1
months ended March 31, 2026, was $0.9 million of non-cash expense related to stock-based compensation expense, including employee stock options, compared to $1.6 million for the three months ended March 31, 2025. The decrease in general and administrative expenses was primarily due to a decrease in stock-based compensation along with a decrease in employee-related expenses.
Net Loss:
For the three months ended March 31, 2026, net loss was $10.4 million, or $0.13 per share compared to $32.1 million, or $0.42 per share, for the prior year period. Included in the net loss for the three months ended March 31, 2026, was $2.0 million of non-cash expenses related to the impact of expensing share-based payments, including employee stock options due in part to fewer employees, as compared to $3.8 million for the same period in 2025.
About Prelude Therapeutics
Prelude Therapeutics is a leading precision oncology company developing innovative medicines in areas of high unmet need for cancer patients. Our pipeline features highly selective KAT6A degraders and JAK2V617F mutant selective inhibitors -- new approaches to clinically validated targets with transformative potential for patients. We are leveraging our expertise in targeted protein degradation to create and develop next generation degrader antibody conjugates (DACs) with novel payloads. We are on a mission to extend the promise of precision medicine to every cancer patient in need. For more information, visit preludetx.com.
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 for Prelude’s product candidates, the potential safety, efficacy, benefits and addressable market for Prelude’s product candidates, the expected timeline for clinical trial results for Prelude’s product candidates, and the sufficiency of Prelude’s cash runway into the second quarter of 2028. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The words “believes,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “potential,” “likely,” “projects,” “continue,” “will,” “schedule,” and “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on the Company’s current expectations and projections about future events and various assumptions. Although Prelude believes that the expectations reflected in such forward-looking statements are reasonable, Prelude 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 Prelude's actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to Prelude's ability to advance its product candidates, the
Exhibit 99.1
receipt and timing of potential regulatory designations, approvals and commercialization of product candidates, clinical trial sites and our ability to enroll eligible patients, supply chain and manufacturing facilities, Prelude’s ability to maintain and recognize the benefits of certain designations received by product candidates, the timing and results of preclinical and clinical trials, Prelude's ability to fund development activities and achieve development goals, Prelude's ability to protect intellectual property, and other risks and uncertainties described under the heading "Risk Factors" in Prelude’s Annual Report on Form 10-K for the year ended December 31, 2025, its Quarterly Reports on Form 10-Q and other documents that Prelude 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 Prelude undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof, except as may be required by law.
Exhibit 99.1
PRELUDE THERAPEUTICS INCORPORATED
STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(UNAUDITED)
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Three Months Ended March 31, |
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(in thousands, except share and per share data) |
2026 |
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2025 |
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Revenue |
$ |
4,580 |
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$ |
— |
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Operating expenses |
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Research and development |
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13,601 |
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28,816 |
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General and administrative |
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5,156 |
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5,790 |
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Total operating expenses |
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18,757 |
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34,606 |
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Loss from operations |
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(14,177 |
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(34,606 |
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Other income, net |
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3,792 |
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2,521 |
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Net loss |
$ |
(10,385 |
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$ |
(32,085 |
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Per share information: |
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Net loss per share of common stock, basic and diluted |
$ |
(0.13 |
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$ |
(0.42 |
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Weighted average common shares outstanding, basic |
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82,519,981 |
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75,986,281 |
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Comprehensive loss: |
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Net loss |
$ |
(10,385 |
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$ |
(32,085 |
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Unrealized loss on marketable securities, net of tax |
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(49 |
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(23 |
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Comprehensive loss |
$ |
(10,434 |
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$ |
(32,108 |
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Exhibit 99.1
BALANCE SHEETS
(in thousands, except share data) |
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March 31, |
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December 31, |
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Assets |
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(unaudited) |
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Current assets: |
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Cash and cash equivalents |
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$ |
21,756 |
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$ |
35,256 |
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Marketable securities |
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59,798 |
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67,958 |
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Prepaid expenses and other current assets |
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3,039 |
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2,478 |
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Total current assets |
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84,593 |
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105,692 |
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Restricted cash |
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3,235 |
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3,235 |
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Property and equipment, net |
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4,722 |
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5,113 |
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Right-of-use asset |
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26,778 |
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27,165 |
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Prepaid expenses and other non-current assets |
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314 |
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110 |
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Total assets |
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$ |
119,642 |
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$ |
141,315 |
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Liabilities and stockholders’ equity |
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Current liabilities: |
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Accounts payable |
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$ |
2,069 |
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$ |
3,983 |
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Accrued expenses and other current liabilities |
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5,938 |
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12,533 |
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Deferred revenue |
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30,952 |
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33,734 |
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Operating lease liability |
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2,761 |
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2,744 |
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Total current liabilities |
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41,720 |
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52,994 |
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Deferred revenue, net of current portion |
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— |
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1,798 |
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Other liabilities |
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2,779 |
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2,841 |
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Operating lease liability |
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14,960 |
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15,045 |
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Total liabilities |
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59,459 |
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72,678 |
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Commitments (Note 8) |
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Stockholders’ equity: |
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Voting common stock, $0.0001 par value: 487,149,741 shares authorized; 48,290,087 and 48,225,493 shares issued and outstanding at March 31, 2026 and December 31, 2025, respectively |
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5 |
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5 |
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Non-voting common stock, $0.0001 par value: 112,850,259 shares authorized; 14,728,135 shares issued and outstanding at both March 31, 2026 and December 31, 2025 |
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1 |
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1 |
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Additional paid-in capital |
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753,664 |
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751,684 |
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Accumulated other comprehensive (loss) income |
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(41 |
) |
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8 |
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Accumulated deficit |
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(693,446 |
) |
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(683,061 |
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Total stockholders’ equity |
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60,183 |
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68,637 |
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Total liabilities and stockholders’ equity |
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$ |
119,642 |
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$ |
141,315 |
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Investor Contact:
Robert A. Doody, Jr.
Senior Vice President, Investor Relations
Prelude Therapeutics Incorporated
484.639.7235
rdoody@preludetx.com
Corporate Presentation May 2026 Exhibit 99.2
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, anticipated discovery, preclinical and clinical development activities for Prelude’s product candidates and milestones, the potential safety, efficacy, benefits and addressable market for Prelude Therapeutic Incorporated's (the "Company") product candidates. 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,’’ “aim,” ‘‘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 filings with the Securities and Exchange Commission, including our Annual Report on Form 10-K for the year ended December 31, 2025. This presentation also contains estimates and other statistical data made by independent parties and by us relating to product growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. This presentation concerns drugs that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration (the "FDA"). They are currently limited by Federal law to investigational use, and no representation is made as to their safety or effectiveness for the purposes for which they are being investigated. Forward Looking Statements & Disclaimers
Kris Vaddi, PhD Chief Executive Officer Andrew Combs, PhD Chief Chemistry Officer Sean Brusky, MBA Chief Business & Strategy Officer Peggy Scherle, PhD Chief Scientific Officer Bryant Lim, J.D. Chief Financial Officer, Chief Legal Officer, Secretary Experienced Leadership Team With Proven Track Record Charles Morris, MD Chief Medical Officer
PROGRAM POTENTIAL INDICATIONS DISCOVERY IND-ENABLING PHASE 1 PROGRAM INTEREST ANTICIPATED MILESTONES JAK2V617F Mutant Selective JH2 Inhibitors VF+ myeloproliferative neoplasms (MPNs) (MF, PV, ET) Phase 1 now enrolling KAT6A Selective Degraders ER+ breast cancer, other malignancies Prelude wholly owned IND filing mid-2026 mCALR DAC CALR-mutated MPNs (ET, MF) Prelude wholly owned Oral abstract presented at ASH 2025 Degrader Payloads for DACs Broad utility across multiple indications . . . Additional Partnerships Prelude’s Pipeline & Discovery Engine JAK2, janus kinase 2; JH2, JAK2 homology domain 2 (pseudokinase regulatory domain); VF+, V617F mutated; MPNs, myeloproliferative neoplasms; MF, myelofibrosis; PV, polycythemia vera; ET, essential thrombocythemia; ER+, estrogen receptor positive; DAC, degrader antibody conjugate; mCALR = mutated calreticulin 1 - Exclusive option agreement with Incyte (Nov. 2025) 2 - DAC Discovery Collaboration with AbCellera (Nov. 2023, amended and expanded 2H 2025) Proprietary degrader payloads available for licensing to partners developing next generation DACs 1 2 PRT12396 PRT13722
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neoplasms (MPNs) KAT6A (PRT13722) Highly Selective Oral Degrader Potentially first-in-class KAT6A degrader with absolute selectivity over KAT6B – a differentiated modality and profile with potential to become a backbone therapy in the treatment of ER+ breast cancer mCALR DAC Next Generation Precision DAC Potentially first-in-class mutated Calreticulin (mCALR) DAC (Degrader Antibody Conjugate) that is equipotent on all CALR mutations and >100x more potent compared to current lead clinical stage CALR antibody
JAK2V617F is the Primary Driver Mutation Leading to Activated JAK-STAT Signaling, Uncontrolled Proliferation, and Disease Progression in MPNs The JAK-STAT pathway mediates growth factor signaling, most notably: Thrombopoietin receptor for platelet production Erythropoietin receptor for red blood cell production The JAK2V617F mutation leads to growth factor-independent hyperactivation of JAK-STAT pathway and uncontrolled myeloid and erythroid proliferation Currently approved JAK inhibitors, like ruxolitinib (Jakafi®), while effective, equally inhibit both WT and V617F-mutated (VF+) JAK2, leading to dose limiting thrombocytopenia and anemia and do not alter disease progression JAK2V617F selective inhibitors target VF+ progenitor cells while sparing normal bone marrow function and offer the potential for disease modification and to transform treatment outcomes for MPN patients Jakafi® is a registered trademark of Incyte Corporation Jakafi® Campbell P.J. and Green A.R. N Engl J Med 2006;355:2452-2466
Prelude Scientists Recently Discovered the First Known JAK2 Inhibitors that Bind in the JAK2 JH2 “Deep Pocket” Where the V617F Mutation Resides Prelude JAK2 JH2 Inhibitors Bind into the “Deep Pocket” Adjacent to V617F Mutation Allosteric JH2 Regulatory Domain vs JH1 Catalytic Domain Confidential
PRT12396 is a JAK2V617F Mutant Selective JH2 Inhibitor with Disease Modifying Potential in MPNs *** p<0.001 by Mann-Whitney U test >200X selectivity over JAK1 and TYK2 and clean profile in KinomeSCAN™ panel of >450 kinases Selective anti-proliferative effects in JAK2VF MPN cells with minimal impact on JAK2WT cells Significant reduction in splenomegaly and normalization of pathogenic cytokines in vivo, equivalent to or better than ruxolitinib in MPN models at well-tolerated doses Isoform selectivity over JAK1/TYK2 Selective inhibition mutant cells in vitro Efficacy in MPN models in vivo BaF3 model ASH Annual Meeting 2025 oral presentation (access here)
No evidence of WT JAK2 inhibition in 2-week rat toxicology study at low and mid doses that provide efficacious exposures Reduction in neutrophils and reticulocytes observed only at high dose, consistent with plasma exposure approaching WT JAK2 IC50 AUC exposures required for efficacy are 10X lower than those associated with bone marrow suppression (reticulocyte inhibition) PRT12396 Demonstrates ~10X Therapeutic Window In Vivo – Potential to Overcome the Limitations of First Generation JAK2 Inhibitors Dotted lines represent proliferation IC50 values from SET2 (VF) and UT-7 (WT) 7-day proliferation assay Reticulocyte Inhibition Only at High Dose, with Full Recovery by Day 15 Efficacy AUC is 10X Lower Than Toxicity AUC Plasma Exposures at Low/Mid Doses Remain Below WT JAK2 IC50 ASH Annual Meeting 2025 oral presentation (access here) Confidential
PRT12396 – Phase 1 Study in MF and PV Cohorts in Parallel – Now Enrolling IND Cleared in January 2026 MF 2026 2027 2028 2029 Phase 1 Expansion Cohorts Phase 1 (MF & PV) First Look at Spleen/Symptoms/CHR Mutant Allele Burden Phase 1a Dose Escalation Expansion Cohorts DL(n) (N=3-6) DL1 (N=3-6) DL2 (N=3-6) Expansion in MF & PV at Dose OBJECTIVE CHR rate, durability (24 week) and molecular response rate (allele burden reduction) Spleen and symptom benefit Data generation in preparation for first registrational trial(s) MPNs, myeloproliferative neoplasms; MF, myelofibrosis; PV, high risk polycythemia vera; CHR, complete hematologic response; DL, dose level PV DL(n) (N=3-6) DL1 (N=3-6) DL2 (N=3-6) Illustrative
Exclusive option agreement with Incyte (announced November 2025) Option Agreement With Incyte Provides Significant Capital to Further Advance Our JAK2V617F and KAT6A Programs
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neoplasms (MPNs) KAT6A (PRT13722) Highly Selective Oral Degrader Potentially first-in-class KAT6A degrader with absolute selectivity over KAT6B – a differentiated modality and profile with potential to become a backbone therapy in the treatment of ER+ breast cancer mCALR DAC Next Generation Precision DAC Potentially first-in-class mutated Calreticulin (mCALR) DAC (Degrader Antibody Conjugate) that is equipotent on all CALR mutations and >100x more potent compared to current lead clinical stage CALR antibody
Selective KAT6A Degradation Could Represent a Differentiated Approach Versus KAT6A/B/(7) Inhibition With Potential for Broader Application Early-stage ER+ BC (adjuvant, neo-adjuvant) KAT6A/B/(7) Inhibitors Pfizer, BeOne, Olema, Ideaya, Menarini, Others 1L ER+/HER2- mBC 2L/3L+ ER+/HER2- mBC Current SoC1 Monotherapy efficacy reported to date with KAT6A/B inhibitors (11% ORR) KAT6B-mediated neutropenia may limit combinability with SoC agents used in the frontline and early-stage settings (e.g., CDK4/6i, PI3K⍺i, etc.) KAT6A Selective Degrader Only KAT6A degrader nearing the clinic Potential for best-in-class monotherapy and combination efficacy KAT6A selectivity may lower neutropenia and enable broad combinability ET +/- CDK4/6 inhibitors ADCs, Targeted Tx ET +/- CDK4/6 inhibitors ET + PI3K⍺ inhibitors +/- CDK4/6i (PIK3CAm) ET +/- CDK4/6 inhibitors Future SoC2 Oral SERDs, CDK2/4 inhibitors, pan-mutant PI3K⍺ inhibitors, ADCs, and other targeted therapies in development 1 - NCCN Treatment Guidelines for Invasive Metastatic and Early Stage Breast Cancer (v5.2025); 2 - clinicaltrials.gov, investor presentations (multiple) ET: Endocrine Therapy, inclusive of SERMs (e.g., tamoxifen), SERDs (e.g., fulvestrant), and aromatase inhibitors (e.g., letrozole, anastrozole, exemestane)
KAT6 is a clinically validated mechanism in ER+ breast cancer A KAT6A/B dual inhibitor, prifetrastat is now in pivotal phase 3 trials in combination with fulvestrant, after progression on a CDK4/6 inhibitor1 Demonstrated compelling efficacy in post CDK4/6 inhibitor setting in a broad population of ER+ BC1 Clinically relevant safety observations including dysgeusia and grade 3/4 neutropenia are challenging and may limit dosing to maximal benefit in combination with SoC treatments (e.g., CDK4/6 inhibitors)1 Our KAT6A program aims to demonstrate a superior clinical profile Optimal efficacy Lower hematological toxicity Improved combinability profile with other agents (e.g., oral SERDs, AIs, CDK4/6is, PI3K⍺is) ER+ breast cancer treatment market is projected to reach $42B by 20332 Most common type of breast cancer, representing 70% of all cases 1 - P LoRusso, et. al,, Dose optimization of PF-07248144, a first-in-class KAT6 inhibitor, in patients (pts) with ER+/HER2− metastatic breast cancer (mBC): Results from phase 1 study to support the recommended phase 3 dose (RP3D) ASCO 2025 Annual Meeting, J Clin Oncol 43, 1020(2025) 2 - Vision Research Reports; "Estrogen Receptor Positive Breast Cancer Treatment Market Forecast 2024-2033. ER+ Breast Cancer Treatment Market Size | Companies Prelude’s First-In-Class Oral KAT6A Selective Degraders
KAT6A: An Emerging Target in the Treatment of ER+/HER2- Breast Cancer 1 - White J, et al. Histone lysine acetyltransferase inhibitors: an emerging class of drugs for cancer therapy. Trends Pharmacol Sci 45 (3): 243-254 (2024). 2 - Sharma S, et al. Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer. Cell Chem Biol 30 (10):1191-1210 (2023). KAT6 is a histone acetyltransferase that epigenetically regulates chromatin accessibility1-2 The KAT6A complex regulates estrogenic, cell cycle, MYC, and other oncogenic pathways1-2 KAT6A and KAT6B are mutually exclusive paralogs, with KAT6A being the primary driver of oncogenesis1-2 KAT6A (8p11) is frequently amplified in breast, lung, and other cancers1-2
PRT13722: Our KAT6A Selective Degrader Development Candidate Absolute selectivity for KAT6A over KAT6B (>1000-fold) based on both degrader kinetics and proteomics Excellent oral PK across species enabling once-daily oral dosing Compelling in vivo efficacy as monotherapy in ER+ BC models, both KAT6A amplified/non-amplified Compelling in vivo efficacy in combo with SoC ET, CDK4/6, PI3K⍺ agents Reduced effect on neutrophils in multiple preclinical models IND filing on track for mid-2026 Absolute Degradation Selectivity (KAT6A vs KAT6B) In Vitro1 KAT6A Amplified ER+/HER2- Breast Cancer CDX Model (ZR-75-1) Dosed with PRT13722* Compelling Monotherapy Efficacy Including Complete Regressions In Vivo1 1 - AACR 2026 poster presentation (access here); CRR = Complete Response Rate; *When denoted with an asterisk, PRT13722* indicates data shown is with the racemic mixture of PRT13722. 63% CRR 100% CRR Global Proteomics
Well-tolerated over treatment duration of 80 days with no observed body weight loss in animals PRT13722 compared to prifetrastat with >50-fold lower AUC at efficacious doses PRT13722 Monotherapy Drives Durable Tumor Regressions in the More Challenging T47-D Model with Improved Efficacy Over prifetrastat + fulvestrant in Combination AACR 2026 poster presentation (access here) 1 - Mice harboring T47-D xenografts were treated with the racemic mixture of PRT13722*; effects on tumor growth are shown. Better Efficacy as Monotherapy vs. prifetrastat + fulvestrant in Combination1 Durable Tumor Regressions Observed at Low Doses (Tumors Below Baseline >2.5 months)1 PRT13722*, 3 mg/kg, PO, QD Class Treatment % Tumors Regressed Mono-Tx prifetrastat, 1 mg/kg 0% PRT13722, 1 mg/kg 50% PRT13722*, 3 mg/kg 75% + ET prifetrastat, 1 mg/kg + fulvestrant 13% PRT13722, 1 mg/kg + fulvestrant 88% Fulvestrant (25 mg/kg, SC, QW+LD)
PRT13722 achieved 100% complete response as a monotherapy in ER+/HER2- xenografts derived from a patient with recurrent disease following treatment with chemotherapy and tamoxifen Responses persisted following cessation of treatment No significant body weight loss observed in animals at either dose level PRT13722 Monotherapy Eradicates Tumors in Post-Tamoxifen Patient-Derived Xenografts (PDX) AACR 2026 poster presentation (access here); Off-tx indicates treatment cessation Treatment Mouse % CRR PRT13722 3 mg/kg, PO, QD 100% (8/8) PRT13722 10 mg/kg, PO, QD 100% (8/8) Tumors at endpoint; CRR = complete response rate (no detectable tumor) PRT13722 Achieved Complete Responses in ST353 PDX Model
PRT13722 Demonstrates Potential for Lower Bone Marrow Toxicity in Preclinical Models Compared to KAT6A/B Dual Inhibitors Ex Vivo Dose Response of CFU-GM LD KAT6A degrader KAT6A selective degraders show limited effects on neutrophils in contrast to dual KAT6A/B inhibitors, supporting potential for improved safety profile and combinability Prelude Data on File; CFU-GM, Colony-Forming Unit-Granulocyte/Macrophage, myeloid progenitor cells found in bone marrow; LD, low dose; HD, high dose; CD, clinical dose *Study conducted with racemic mixture of PRT13722; AACR 2026 poster presentation (access here) In Vivo Neutrophil Assessment (Day 5) KAT6A degrader Plot of In Vivo Efficacy vs. Impact on CFU-GM Viability (PRT13722 vs. prifetrastat) HD HD LD CD
PRT13722 Demonstrates Synergistic Potential in Combination with Current SoC Agents (ET, CDK4/6i, PI3Kαi) In Vivo Deeper monotherapy and combination efficacy H2H vs. prifetrastat at clinical doses Excellent in vivo efficacy in combination with fulvestrant (ET), alpelisib (PI3Kαi) and abemaciclib (CDK4/6i) No dosing holidays, body weight loss, mortality, or adverse clinical signs, alone or in combination AACR 2026 poster presentation (access here) prifetrastat Current Standard of Care Agents fulvestrant (ET/SERD) abemaciclib (CDK4/6i) alpelisib (PI3Kαi) PRT13722 1 mg/kg
Prelude is advancing a potenial first-in-class, highly selective oral KAT6A degrader (PRT13722) with potential to become a new backbone therapy in the treatment of ER+/HER2- breast cancer PRT13722 has potential to achieve more robust efficacy relative to KAT6A/B/(7) inhibitors PRT13722 was well-tolerated, supporting potential to differentiate further based on overall safety and combinability with other agents On track for IND filing in mid-2026 with Phase 1 study start expected in 2H 2026 KAT6A Selective Degrader Program Summary
Our Investment Thesis Centers on Advancing Highly Differentiated Approaches to Clinically Validated Targets JAK2V617F (PRT12396) Mutant Selective Inhibitors Potentially transformative JAK2V617F allosteric JH2 inhibitor with potential to reduce mutant allele burden and modify the course of disease progression in patients with myeloproliferative neoplasms (MPNs) KAT6A (PRT13722) Highly Selective Oral Degrader Potentially first-in-class KAT6A degrader with absolute selectivity over KAT6B – a differentiated modality and profile with potential to become a backbone therapy in the treatment of ER+ breast cancer mCALR DAC Next Generation Precision DAC Potentially first-in-class mutated Calreticulin (mCALR) DAC (Degrader Antibody Conjugate) that is equipotent on all CALR mutations and >100x more potent compared to current lead clinical stage CALR antibody
Mutated Calreticulin (mCALR) Represents a Promising Target for Next Generation DACs Mutant CALR is a neoantigen presented on the cell surface of malignant cells but not normal cells and is found in 25-35% of patients with Myelofibrosis (MF) and ET SMARCA2/4 degraders are highly active in CALR mutated MPN cell lines and can be used as payloads for mCALR-targeted DACs mCALR-targeted DACs, delivering Prelude’s degrader payloads to disease-initiating clones have the potential for a differentiated approach for mCALR+ MPNs Primary Myelofibrosis (PMF) Essential Thrombocythemia (ET) Polycythemia Vera (PV) JAK2 V617F Mutated ~95% MPL mutation MPL mutation Nonmutated Nonmutated mCALR is emerging as a clinically validated target in MPNs with disease modifying potential Nonmutated ~5,000 ~32,500 N/A Est. # of US Pts. with CALR Mutation Sources: NCI SEER Database (accessed Dec 2024), Leukemia & Lymphoma Society Facts & Figures; J.How et. al., Mutant calreticulin in myeloproliferative neoplasms, Blood (2019) 134 (25): 2242–2248 JAK2 V617F Mutated ~95% JAK2 V617F Mutated ~60% JAK2 V617F Mutated ~55% CALR Mutated ~35% CALR Mutated ~25%
Precision Degrader Antibody Conjugates (pDACs) Represent Next Generation ADCs For a review of ADCs, see Fu, Z., Li, S., Han, S. et al. Sig Transduct Target Ther 7, 93 (2022). Precision DACs enable improved selectivity in two ways Antibodies target tumor-specific cell surface antigens sparing healthy cells, and Targeted Protein Degraders address critical proteins in validated biological pathways Potential to deliver both improved efficacy and improved tolerability Property Traditional ADC Precision DAC Potency Antibody Selectivity Payload Selectivity PD Marker - Payload Non-Genotoxic X X X TPDs Remain an Under-represented Payload Class* *Data source: Morris, J. Beacon ADC by HansonWade. “Analyzing the ADC Boom: Landscape Review.” World ADC (San Diego). November 2024. Denotes Payload MOA for clinical stage assets currently in development at time of analysis.
Prelude Discovered mCALR x SMARCA2/4 DACs With Robust and Selective in vitro and in vivo Activity and ~100x Improved Potency in CALR Mutant Cells >68x Selective Cytotoxicity in vitro SMARCA2/4 Degrader Robust Tumor Growth Inhibition in vivo Fultang N., et al., EHA2025 Oral Abstract, 12 June 25; Discovery Of First-in-class Precision ADCs Targeting Mutant Calreticulin For The Treatment Of MPNs. (access here); Reis, et al. Blood. 2024;144(22):2336 CALR x SMARCA2/4 DAC CALR x SMARCA2/4 DAC DAC Naked Ab ~100x Better Potency
Executive Summary Lead JAK2V617F mutant selective inhibitor (PRT12396) IND cleared and Phase 1 study enrollment underway1 Potentially first-in-class KAT6A selective degrader (PRT13722) on track to enter the clinic in 2026 with a path to differentiation in ER+/HER2- breast cancer market Novel approaches to clinically-validated targets (e.g., mCALR) poised to deliver differentiated pipeline candidates beyond JAK2 and KAT6A Current cash runway expected into second quarter of 2028 based on preliminary estimates, driven by previously announced underwritten offering with gross proceeds of $90 million 1 - Subject of exclusive option agreement with Incyte (announced November 2025)
Thank You Contact Us: Robert Doody SVP, Investor Relations rdoody@preludetx.com