RLAY 8-K
Relay Therapeutics, Inc. (RLAY)
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): |
(Exact name of Registrant as Specified in Its Charter)
(State or Other Jurisdiction |
(Commission File Number) |
(IRS Employer |
||
|
|
|
|
|
|
||||
|
||||
(Address of Principal Executive Offices) |
|
(Zip Code) |
||
Registrant’s Telephone Number, Including Area Code: |
|
(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:
Securities registered pursuant to Section 12(b) of the Act:
|
|
Trading |
|
|
|
|
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 7.01 Regulation FD Disclosure.
On April 27, 2026, Relay Therapeutics, Inc. (the "Company") issued a press release announcing clinical data from the zovegalisib, fulvestrant and atirmociclib triplet combination arm of the Phase 1/2 ReDiscover trial as well as the Company's plans to move zovegalisib plus atirmociclib into Phase 3 development for frontline ("1L") patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer, a copy of which is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K. The Company hosted a conference call and live webcast to discuss the clinical data and Phase 3 development plans on April 27, 2026 at 8:30 a.m. E.T. The Company has made available a slide presentation to accompany the call, a copy of which is being furnished as Exhibit 99.2 to this Current Report on Form 8-K. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.2.
The information in this Item 7.01, including Exhibit 99.1 and Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed "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, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such filing.
Item 8.01 Other Events.
On April 27, 2026, the Company announced clinical data from the zovegalisib, fulvestrant and atirmociclib triplet combination arm of the Phase 1/2 ReDiscover trial as well as the Company's plans to move zovegalisib plus atirmociclib into Phase 3 development for 1L patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer.
Triplet Clinical Data
Zovegalisib is currently being evaluated in the ReDiscover trial, an ongoing first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of zovegalisib in combination with fulvestrant and CDK inhibitors in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. These data are from the zovegalisib plus atirmociclib plus fulvestrant dose finding portion of the trial.
As of the April 13, 2026 data cut-off date (the "Data Cut-Off Date"), 69 total patients were enrolled, with 62 patients at or below the potential Phase 3 dose and 34 patients with measurable disease evaluable for response. All patients had previously received a CDK4/6 inhibitor and at least one prior endocrine therapy in the advanced setting and could have received a PI3K pathway inhibitor. These heavily pre-treated patients had received a median of two prior therapies (21% received three or more prior therapies) in the metastatic setting with 63% having visceral disease, 29% having received chemotherapy, and 47% being pre-diabetic. The median follow-up was 7.4 months.
Early safety and tolerability data for zovegalisib in combination with atirmociclib and fulvestrant (N=62) reinforce the potential of this regimen moving forward in 1L endocrine sensitive patients. As of the Data Cut-Off Date:
As of the Data Cut-Off Date, 34 patients had measurable disease to be evaluated for response:
Pharmacokinetic analyses demonstrated that atirmociclib increased the exposure of zovegalisib by about two and half-fold (regardless of atirmociclib dose), while zovegalisib had no impact on atirmociclib exposure. Subject to regulatory feedback, the potential Phase 3 dose of zovegalisib will be 150mg twice daily (BID), which maintains average concentration of zovegalisib just below IC90 throughout the dosing interval.
Preliminary Phase 3 Development Plans
The planned study, subject to regulatory feedback, is a randomized Phase 3 trial evaluating zovegalisib in combination with atirmociclib and aromatase inhibitor ("AI") in 1L endocrine sensitive patients with PIK3CA-mutated, HR+/HER2- advanced or metastatic breast cancer.
Pursuant to the terms of a clinical trial supply agreement, Pfizer, Inc. ("Pfizer") has agreed to supply atirmociclib for the experimental arm in combination with zovegalisib and the palbociclib portion of the control arm for use in the planned study. The Company will sponsor, fully operationalize and fund the planned Phase 3 trial.
Cautionary Note Regarding Forward Looking Statements
This Current Report on Form 8-K and certain materials furnished or filed herewith contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the Company's strategy, business plans and focus; the progress and timing of the clinical development of the programs across the Company's portfolio, including the timing of initiation of a frontline Phase 3 clinical trial for zovegalisib in combination with atirmociclib and AI; the timing of clinical data readouts for zovegalisib; the expected therapeutic benefits and potential efficacy and tolerability of zovegalisib, both as a monotherapy and in combination with other agents, including the combination of zovegalisib and atirmociclib, and its other programs; the clinical data for zovegalisib; the interactions with regulatory authorities and any related approvals; the potential commercialization and market opportunity for zovegalisib; and the expected strategic benefits under the Company's clinical trial supply agreement with Pfizer. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements in this Current Report on Form 8-K are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which the Company has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; significant political, trade or regulatory developments, such as tariffs, beyond the Company's control; the delay or pause of any current or planned clinical trials or the development of the Company's drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; the Company's ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in the Company's most recent Annual Report on Form 10-K, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent the Company's views only as of today and should not be relied upon as representing its views as of any subsequent date. The Company explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Item 9.01 Financial Statements and Exhibits.
99.1 |
Press release issued by Relay Therapeutics, Inc. on April 27, 2026, furnished herewith. |
99.2 |
Corporate presentation, dated April 27, 2026, furnished herewith. |
104 |
Cover Page Interactive Data File (embedded within Inline XBRL document) |
SIGNATURES
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.
|
|
|
RELAY THERAPEUTICS, INC. |
|
|
|
|
Date: |
April 27, 2026 |
By: |
/s/ Soo-Yeun Lim |
|
|
|
Soo-Yeun Lim |
Exhibit 99.1
Relay Therapeutics Announces Clinical Data for Zovegalisib plus Atirmociclib Triplet Combination Supportive of Further Development in Frontline Metastatic Breast Cancer
Zovegalisib + atirmociclib + AI selected as triplet regimen for frontline development
Compelling efficacy and tolerability data for zovegalisib triplet in median 3L patients
44% ORR in heavily pre-treated, CDK4/6-experienced patients (median third-line); ORR is similar across kinase and non-kinase PIK3CA mutations
Phase 3 frontline trial in endocrine sensitive patients expected to initiate in early 2027, subject to regulatory feedback
Supply agreement in place with Pfizer to supply atirmociclib for the Phase 3 frontline trial
Relay Therapeutics to host a conference call today, April 27, at 8:30am ET
Cambridge, Mass. – April 27, 2026 – Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease, today announced plans to move zovegalisib + atirmociclib, Pfizer’s investigational, potential first-in-class CDK4 inhibitor, into Phase 3 development for frontline patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer.
“While PI3Kα inhibition has demonstrated meaningful benefit in breast cancer, its use in the frontline setting has been limited by tolerability challenges with earlier agents,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “We believe that combining the selective profiles of zovegalisib and atirmociclib with endocrine therapy has the potential to enable a well-tolerated, all-oral triplet regimen, and these initial data support advancing this combination into Phase 3 development for patients with frontline metastatic breast cancer.”
Zovegalisib + Atirmociclib Data Demonstrate Potential Best-in-Class Triplet Profile
Zovegalisib is currently being evaluated in ReDiscover, an ongoing first-in-human study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of zovegalisib in combination with fulvestrant and CDK inhibitors in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. These data are from the zovegalisib + atirmociclib + fulvestrant dose finding portion of the study.
As of the April 13, 2026 data cut-off date, 69 total patients were enrolled, with 62 patients at or below the potential Phase 3 dose and 34 patients with measurable disease evaluable for response. All patients had previously received a CDK4/6 inhibitor and at least one prior endocrine therapy in the advanced setting and could have received a PI3K pathway inhibitor. These heavily pre-treated patients had received a median of 2 prior therapies (21% received 3+ prior therapies) in the metastatic setting with 63% having visceral disease, 29% having received chemotherapy, and 47% being pre-diabetic. The median follow-up was 7.4 months.
Expansion cohorts of zovegalisib + atirmociclib + fulvestrant and zovegalisib + atirmociclib + aromatase inhibitor (AI) in the ReDiscover study are ongoing.
Safety and Tolerability of Triplet is Critical for Potential Long-Term Treatment in Frontline Endocrine Sensitive Breast Cancer
Early safety and tolerability data for zovegalisib in combination with atirmociclib and fulvestrant (N=62) reinforce the potential of this regimen moving forward in frontline endocrine sensitive patients. As of the April 13, 2026 data cut-off date:
Overall Response Rate in Median Third Line Patients is Approaching ORR Seen in Frontline Breast Cancer with Standard of Care
As of the April 13, 2026 data cut-off date, 34 patients had measurable disease to be evaluated for response:
Pharmacokinetics
Pharmacokinetic analyses demonstrated that atirmociclib increased the exposure of zovegalisib by about two and half-fold (regardless of atirmociclib dose), while zovegalisib had no impact on atirmociclib exposure. Subject to regulatory feedback, the potential Phase 3 dose of zovegalisib will be 150mg twice daily (BID), which maintains average concentration of zovegalisib just below IC90 throughout the dosing interval.
Preliminary Phase 3 Trial Design in Frontline Endocrine Sensitive Patients
The planned study, subject to regulatory feedback, is a randomized Phase 3 trial evaluating zovegalisib in combination with atirmociclib and aromatase inhibitor (AI) in frontline endocrine sensitive patients with PIK3CA-mutated, HR+/HER2- advanced or metastatic breast cancer.
Pfizer to Supply Atirmociclib and Palbociclib Through Supply Agreement
Pfizer has agreed to supply atirmociclib for the experimental arm in combination with zovegalisib and the palbociclib portion of the control arm for use in the planned study. Relay Tx will sponsor, fully operationalize and fund the planned Phase 3 trial. Relay Tx retains full global rights for zovegalisib.
Next Steps
Conference Call Information
Relay Therapeutics will host a conference call and live webcast today, April 27, at 8:30 a.m. ET. Registration and dial-in for the conference call may be accessed through Relay Therapeutics’ website under Events in the News & Events section through the following link: https://ir.relaytx.com/news-events/events-presentations. An archived replay of the webcast will be available following the event.
About Zovegalisib
Zovegalisib is the lead program in Relay Therapeutics’ efforts to discover and develop mutant selective inhibitors of PI3Kα, the most frequently mutated kinase in all cancers and all vascular anomalies. Zovegalisib has the potential, if approved, to address a significant portion of the approximately 140,000 patients with HR+/HER2- breast cancer with a PI3Kα mutation and the estimated 170,000 patients with vascular anomalies driven by a PI3Kα mutation per year in the United States, one of the largest patient populations for a precision medicine.
Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric, site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type (WT) PI3Kα and off-isoform activity. Toxicity related to inhibition of WT PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. The Dynamo® platform enabled the discovery of zovegalisib, the first known allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, designed to overcome these limitations. Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between WT and mutant PI3Kα, and leveraged these insights to support the design of zovegalisib. Zovegalisib is currently being evaluated in multiple metastatic breast cancer studies and a first-in-human study designed to treat patients with PIK3CA (PI3Kα) mutation driven vascular anomalies. For more information on zovegalisib, please visit here.
About Relay Therapeutics
Relay Therapeutics (Nasdaq: RLAY) is a clinical-stage, small molecule precision medicine company developing potentially life-changing therapies for patients living with cancer and genetic disease. Relay Therapeutics’ Dynamo® platform integrates an array of leading-edge computational and experimental approaches designed to drug protein targets that have previously been intractable or inadequately addressed. The company’s lead clinical asset, zovegalisib, is the first pan-mutant selective PI3Kα inhibitor to enter clinical development and is currently in a Phase 3 clinical trial (ReDiscover-2) in HR+/HER2- metastatic breast cancer. Zovegalisib is also being investigated in a group of genetic disease indications called PI3Kα-driven vascular anomalies. Relay Therapeutics’ pipeline also includes programs for NRAS-driven solid tumors and Fabry disease. For more information, please visit www.relaytx.com or follow us on LinkedIn.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Relay Therapeutics’ strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics’ portfolio, including the timing of initiation of a frontline Phase 3 clinical trial for zovegalisib in combination with atirmociclib and AI; the timing of clinical data readouts for zovegalisib; the expected therapeutic benefits and potential efficacy and tolerability of zovegalisib, both as a monotherapy and in combination with other agents, including the combination of zovegalisib and atirmociclib, and its other programs; the clinical data for zovegalisib; the interactions with regulatory authorities and any related approvals; the potential commercialization and market opportunity for zovegalisib; and the expected strategic benefits under Relay Therapeutics' clinical trial supply agreement with Pfizer. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which Relay Therapeutics has operations or does business, as well as on the timing and anticipated results of its clinical trials, strategy, future operations and profitability; significant political, trade or regulatory developments, such as tariffs, beyond Relay Therapeutics’ control; the delay or pause of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary or interim results of its preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of its product candidates and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; Relay Therapeutics’ ability to successfully demonstrate the safety and efficacy of its drug candidates; the timing and outcome of its planned interactions with regulatory authorities; and obtaining, maintaining and protecting its intellectual property. These and other risks and uncertainties are described in greater
detail in the section entitled “Risk Factors” in Relay Therapeutics’ most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Relay Therapeutics' views only as of today and should not be relied upon as representing its views as of any subsequent date. Relay Therapeutics explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements.
Contact:
Pete Rahmer
Media:
Dan Budwick
1AB
973-271-6085
Zovegalisib Triplet Disclosure April 2026 Exhibit 99.2
Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding the progress and timing of the clinical development of the programs across our portfolio, including the expected timing of data readout and other clinical and developmental milestones; the expected therapeutic benefits of our programs, and potential efficacy and tolerability; the timing of clinical data updates across our pipeline, including the progress of doublet and triplet combinations for zovegalisib (RLY-2608) and the timing of clinical updates for zovegalisib, including with respect to the ReDiscover, ReDiscover-2 and ReInspire clinical trials; the timing of clinical initiation of our various programs, including clinical development of our non-inhibitory chaperone for Fabry disease, and clinical development of our NRAS-selective inhibitor; the potential of our product candidates to address a major unmet medical need; expectations regarding our pipeline, operating plan, use of capital, expenses and other financial results; our cash runway projection; the competitive landscape and potential commercialization and market opportunities for our product candidates; the expected strategic benefits under our collaborations; our ability to successfully establish or maintain collaborations or strategic relationships for our product candidates; expectations regarding current and future interactions with the U.S. Food and Drug Administration (FDA) or other regulatory authorities and any related approvals; our ability to manufacture our product candidates in conformity with the FDA’s requirements; the capabilities and development of our Dynamo®️ platform, including its role in identifying product candidates; our plans to develop, manufacture and commercialize our current product candidates and any future product candidates; and the implementation of our business model and strategic plans for our business, current product candidates and any future product candidates. The words “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this presentation are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this presentation, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability and conflicts, or public health epidemics or outbreaks of an infectious disease on countries or regions in which we have operations or do business; significant political, trade, or regulatory developments, such as tariffs, beyond our control; the timing and anticipated results of our clinical trials, strategy, future operations and profitability; the delay or pause of any current or planned clinical trials or the development of our drug candidates; the risk that the preliminary results of our preclinical or clinical trials may not be predictive of future or final results in connection with future clinical trials of our product candidates; our ability to successfully demonstrate the safety and efficacy of our drug candidates; the timing and outcome of our planned interactions with regulatory authorities; and obtaining, maintaining and protecting our intellectual property. These and other risks, uncertainties and important factors are described in the section entitled "Risk Factors" in our most recent Annual Report on Form 10-K and Quarterly Report on Form 10-Q, as well as any subsequent filings with the Securities and Exchange Commission. Any forward-looking statements represent our views only as of the date of this presentation and we undertake no obligation to update or revise any forward-looking statements, whether as a result of new information, the occurrence of certain events or otherwise. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third-party sources. In addition, no independent source has evaluated the reasonableness or accuracy of our internal estimates or research and no reliance should be made on any information or statements made in this presentation relating to or based on such internal estimates and research. This presentation contains trademarks, trade names and service marks of other companies, which are the property of their respective owners.
Zovegalisib – Potential To Address 3 Large Commercial Opportunities $2-3B $7-8B $6-8B 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Note: TAM calculated based on market benchmarks and internal analysis Estimated US TAM
2L Breast Cancer – Ph1/2 Data at Ph3 Dose Showed Clinically Meaningful PFS 2L Breast Cancer $2-3B Capivasertib + Fulv (4 days on, 3 off) Zovegalisib + Fulv 400mg BID (Phase 3 Dose) Ph3 regimens Zovegalisib shows favorable efficacy in 2L+ patients Interim zovegalisib data support ongoing Phase 3 trial against capivasertib 2L & 3L+ Post-CDK4/6 ORR: 43% ORR: 26% 5.5mo mPFS 11.1mo mPFS 11.2mo in Kinase | 11.0mo in Non-Kinase Sources: ReDiscover Ph1/2 preliminary data as of 1/13/2026; Capi + fulv Ph3 data from CAPItello-291, Turner N Engl J Med 2023; 388:2058-2070. Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted.
1L Breast Cancer – Establishing Zovega + Atirmo + AI Combinability for 1L Use 44% ORR Standard of Care CDK4/6 + ET vs. 40% Gr3+ AE 50-90% Gr3+ AE vs. Zovega + Atirmo + ET selected as go-forward 1L regimen; Supply agreement signed with Pfizer for atirmo Trial intended to initiate in early 2027 Efficacy Tolerability Zovega + Atirmo + ET Triplet Doublet ReDiscover preliminary data as of 04/13/2026 53-55% ORR Study Population 1L Patients Median 3L Patients vs. 1L Breast Cancer $7-8B
Vascular Anomalies – First Clinical Data to be Presented in May at ISSVA Vascular Anomalies $6-8B International Society for the Study of Vascular Anomalies ISSVA World Congress 2026 May 19-22 Philadelphia, PA Abstract Accepted Presentation on Wednesday May 20, 2026, at 4pm ET
Zovegalisib – Potential To Address 3 Large Commercial Opportunities Note: TAM calculated based on market benchmarks and internal analysis $2-3B $7-8B $6-8B 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Estimated US TAM
1L Breast Cancer – Large Commercial Market ~35,000 Patients 1L Breast Cancer (PIK3CA mutated) Large Existing CDK4/6 Market in 1L+ ~$3B ~$4B ~$3B Estimated global sales in metastatic setting2 1. Decision Resources Group market forecast G7 drug treated HR+/HER2- patients totals ~84,000 in 2026, assume 40% PIK3CA-mut (March 2026) ; 2. Global sales estimations for 2026 Evaluate Pharma, March 2026. Patients in G7 markets1 1L Breast Cancer
PIK3CA Mutant Inhibition Provides Clear Benefit in 1L Breast Cancer <$150M annual sales in 20253 despite proven OS benefit Non-selective PI3Kα inhibitor has shown PFS & OS benefit in 1L INAVO1201: 1L Endocrine Resistant 91% Gr3+ AE rate1 “Dear Dr.” letter for ketoacidosis2 1L Breast Cancer Inavolisib + palbo + fulv placebo + palbo + fulv vs. Opportunity to improve outcomes for PIK3CAmut patients in 1L PFS HR: 0.42 (17.2mo vs. 7.3mo) OS HR: 0.67 (34.0mo vs. 27.0mo) However, toxicity is limiting; inavolisib not broadly used in 1L Sources: 1. INAVO120: Jhaveri 2025, N Engl J Med 2025;393:151-161; 2. Genentech Important Drug Warning, March 2025; 3. Company financial results
Zovegalisib – Establishing 1L Triplet Combinability in Median 3L Patients Ideal 1L Profile of Zovegalisib Triplet Superior efficacy Comparable tolerability Supportive data from median 3L patients: Triplet similar ORR in median 3L vs. CDK4/6 + ET doublet ORR in 1L Triplet toxicity profile appropriate for long-term 1L use 1L Breast Cancer Current ongoing zovegalisib triplet dose finding in 2L+ patients CDKi + Zovega + ET
50-90% Gr3+ AE 53-55% ORR 1L Breast Cancer – Demonstrating Zovega + Atirmo + AI Combinability Standard of Care CDK4/6 + ET Zovega + Atirmo + ET Zovega + Atirmo + ET selected as go-forward 1L regimen; Trial intended to initiate in early 2027 Triplet Doublet ReDiscover preliminary data as of 04/13/2026 44% ORR vs. 40% Gr3+ AE vs. Efficacy Tolerability Study Population vs. 1L Patients Median 3L Patients 1L Breast Cancer
Zovegalisib – Laying the Foundation for Potential Next-Gen 1L Combos 1L Breast Cancer Zovegalisib Zovegalisib Zovegalisib + + + Atirmociclib (CDK4-selective) Ribociclib (CDK4/6i) Palbociclib (CDK4/6i) + + + fulvestrant fulvestrant fulvestrant Zovega + Atirmo + ET Selected as preferred go-forward regimen for 1L Phase 3 trial Ph1 arms for triplet combinations (in 2L+ patients) 1. FourLight-1 evaluates atirmociclib + fulvestrant vs. fulvestrant or everolimus + exemestane Recent topline readout for FourLight-1 trial1: Atirmo + fulv in 2L patients 0.6 Hazard Ratio Only 6% discontinued due TEAE
Positive Drug Interaction Observed Zovegalisib Triplet – Dose Escalation Dose Escalation 1L Breast Cancer Zovega Exposure Dosing Interval Zovega + atirmo + fulv ~2.5x higher exposures of zovega with atirmo ReDiscover preliminary data as of 04/13/2026 The following data is for 62 patients dosed with zovega + atirmo triplet (median follow-up 7.4mo) excludes 200mg BID zovega + 300mg BID atirmo dose which is deprioritized for further development (N=7) 100mg BID Zovega 150mg BID Zovega 200mg BID Zovega + atirmo (100-300mg) + fulvestrant Zovega + fulv Zovega exposures ~2.5x higher in atirmo triplet combo than in fulvestrant doublet at same dose Atirmociclib exposures are not impacted by zovega Phase 3 dose, pending regulatory feedback
Zovegalisib + Atirmociclib Triplet – Demographics 1. Baseline HbA1c ≥5.7, glucose ≥100, or medical history of pre-diabetes mellitus; 2. Visceral metastatic sites include brain, lung, liver, pleural, peritoneal involvement; 3. 3 patients received prior CDK4/6 in the adjuvant setting which is allowed per protocol; 4. Percentage was based on pts with evaluable ctDNA data at baseline. ECOG = Eastern Cooperative Oncology Group performance status Median 3L with 21% of patients 4L+ (zovega doublet data is median 2L) 1L Breast Cancer Nearly half of patients are pre-diabetic ReDiscover preliminary data as of 04/13/2026 Zovegalisib + Atirmociclib + Fulvestrant (n=62) Age, Median (Range), Years 61.5 (33, 79) ECOG, 0 / 1, n (%) 45 (72.6) / 17 (27.4) Local PIK3CA Baseline Results Kinase Mutation, n (%) 33 (53.2) Non-Kinase Mutations, n (%) 29 (46.8) Pre-diabetic1 n (%) 29 (46.8) Measurable Disease, n (%) 38 (61.3) Patients with Visceral Metastases, n (%)2 39 (62.9) Prior Lines of Therapy in Advanced Setting, n (%) 2 0 2 (3.2) 1 28 (45.2) 2 19 (30.6) 3+ 13 (21.0) Prior Therapies in Advanced Setting CDK4/6, n (%)3 59 (95.2) Fulvestrant or Novel SERD, n (%) 36 (58.1) Chemo / ADC, n (%) 18 (29.0) PI3Ki / AKTi, n (%) 10 (16.1) ESR1 Mutation4, n (%) 22/53 (41.5)
Dose proportional exposures of zovegalisib above IC80 Drug interaction observed Zovegalisib PK Profiles with Atirmociclib + Fulvestrant 1L Breast Cancer Zovega Exposure Dosing Interval Zovega + fulv Zovega + atirmo + fulv ~2.5x higher exposures of zovega with atirmo 200mg zovega (atirmo triplet) 150mg zovega (atirmo triplet) 100mg zovega (atirmo triplet) ReDiscover preliminary data as of 04/13/2026 All triplet doses shown are with 300mg BID atirmo Atirmociclib exposures are not impacted by zovega All zovega doses above IC80
Zovegalisib + Atirmociclib Triplet – Efficacy in Median 3L Patients ReDiscover preliminary data as of 04/13/2026 2 patients (1 was pre-treated with PI3K pathway inhibitors) who discontinued prior to first post-baseline scan were included in the denominator, which are not shown; ORR includes 2 unconfirmed PR 1L Breast Cancer uCR was a confirmed PR * Responses across mutation types: Kinase: 44% (8/18) Non-Kinase: 44% (7/16) at or below possible Ph3 doses SoC doublet: 53-55% ORR in 1L vs. 44% ORR in median 3L (15/34) Median 3L patients 21% of patients saw prior PI3K pathway inhibitors
Zovega + Atirmo + Fulv1 Zovega Triplet Efficacy Compared Favorably to CDK Regimens in 1L and 2L+ Median 3L: Zovega + Atirmo + Fulv 2L+: Inavo + CDK4/6 + Fulv 1L Breast Cancer Triplet in 2L+ ORR (%) 44% ORR in median 3L 1L Endocrine Resistant: Inavo + Palbo + Fulv 1L Endocrine Sensitive: CDK4/6 + AI Doublet Ribo + AI3 Abema + AI4 Approved Regimens in 1L mPFS 25mo 28mo 17mo Inavo + Palbo + Fulv5 Zovega + atirmo triplet ORR in median 3L was similar to rates of 1L SoC 1. ReDiscover preliminary data as of 04/06/2026; 2. MORPHEUS trial SABCS 2025, PD10-08; 3. KISQALI package insert, Novartis Pharmaceuticals; 2017, and Annals of Oncology 29: 1541–1547 (2018); 4. VERZENIO package insert, Eli Lilly and Company (2017); 5. ITOVEBI package insert, Genentech USA, Inc., A Member of the Roche Group (2024). Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. Inavo + 600mg ribo + fulv2 Inavo + abema + fulv2 ReDiscover preliminary data as of 04/13/2026
Zovegalisib – TRAEs ≥15% 1L Breast Cancer TRAE ≥15% 40% Gr3+ TRAEs Low rates of dose reduction and discontinuation Dose reduction of zovega due to TRAE: 6 patients (9.7%) Dose discontinuation of zovega due to TRAE: 2 patients (3.2%) Diarrhea occurred intermittently & was readily managed with oral antidiarrheal ReDiscover preliminary data as of 04/13/2026 Zovegalisib + Atirmociclib + fulvestrant (N=62) All Gr Gr1 Gr2 Gr3+ Diarrhea 58% 34% 18% 7% Neutropenia1,2 48% 5% 18% 26% Fatigue2 42% 26% 13% 3% Rash2 34% 19% 8% 7% Nausea 26% 23% 2% 2% Alopecia 24% 21% 3% - Hyperglycemia2 23% 18% 5% - White Blood Cell Count Decrease 18% 5% 7% 7% Dry Skin 16% 15% 2% - Hypokalemia1,2 15% 8% 5% 2% Median 3L Note: 1: 1 patient with Gr4 neutropenia; 1 pt with G4 hypokalemia 2: Hyperglycemia includes Preferred Terms (PT): Hyperglycemia and Blood Glucose Increased; Neutropenia includes Neutropenia and Neutrophil Count Decreased; Fatigue includes the PTs: Fatigue, and Asthenia; Hypokalemia includes the PTs: Hypokalemia and Blood Potassium Decreased; Rash includes the PTs: Rash, Rash Macular, Rash Maculo-Papular.
Zovega + Atirmo + Fulv1 Zovega Triplet Safety Compared Favorably to CDK Regimens in 1L and 2L+ Median 3L: Zovega + Atirmo + Fulv 2L+: Inavo + CDK4/6 + Fulv 1L Breast Cancer Triplet in 2L+ Gr3+ AE (%) 1L Endocrine Resistant: Inavo + Palbo + Fulv 1L Endocrine Sensitive: CDK4/6 + AI Doublet Ribo + AI3 Abema + AI4 Approved Regimens in 1L Inavo + Palbo + Fulv5 Zovega + atirmo triplet AE rate is lower than that of 1L SoC Inavo + 600mg ribo + fulv2 Inavo + abema + fulv2 ReDiscover preliminary data as of 04/13/2026 40% Gr3+ AE in median 3L PI3Ki Dose Reductions 33% 47% 9.7% 1. ReDiscover preliminary data as of 04/13/2026; 2. MORPHEUS trial SABCS 2025, PD10-08; 3. MONALEESA-2, Hortobagyi, GN et al, N Engl J Med 2016;375:1738-48; 4. MONARCH-3, Goetz MP et al, J Clin Oncol 35, 3638-3646(2017); 5. INAVO120, Turner et al, N Engl J Med 2024;391:1584-1596. . Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted.
Zovegalisib + Atirmociclib Triplet – Swimlane ReDiscover preliminary data as of 04/13/2026 1L Breast Cancer Cycle Median follow-up: 7.4mo 48/62 (77%) patients ongoing Median PFS not reached
Key endpoints: Preliminary 1L Metastatic HR+/HER2- Breast Cancer Trial Schema Zovegalisib + Atirmociclib + AI CDK4/6 (investigator’s choice) + AI HR+, HER2- advanced / met BC PIK3CA mutation No prior line of tx in adv/met setting Endocrine sensitive Key eligibility criteria: mPFS (primary) OS (key secondary) Preliminary Trial Design (subject to regulatory feedback) R 1:1 1L Breast Cancer
Zovegalisib (RLY-2608) – Multiple Future Potential Development Options PIK3CA-mutated Breast Cancer 1L Breast Cancer HR+/HER2- HER2+ TNBC Zovega + ET (+/- CDK) Zovega + CDK + ET Zovega + ET1 (select populations) Zovega + fulv Zovega + Oral SERD 1. Patients who had early disease relapse on adjuvant CDK4/6 are eligible for ongoing ReDiscover-2 trial; 2. Decision Resources Group market forecast G7 drug treated HR+/HER2- patients totals ~84,000 in 2026, assume 40% PIK3CA-mut (March 2026) Zovega + HER2-targeted +/- ET Zovega + chemo/IO Adjuvant 1L 2L+ Patients in G7 markets2 Opportunity Size: 1L PIK3CAm ~35k patients ~10k patients ~5k patients
Clinical Trial Supply Agreement with Pfizer and Next Steps Plan for regulatory interaction in 2026 Aim to initiate Phase 3 trial in 1L Breast Cancer in early 2027 Relay to sponsor, fully operationalize, and fund 1L Phase 3 trial Relay retains full global rights for zovegalisib Pfizer supplies atirmociclib for experimental arm & palbociclib for control arm 1L Breast Cancer
Relay Tx – Clear Path to Addressing Large Commercial Opportunities 1. Clinical benchmark references: 2L breast cancer: capivasertib + fulvestrant (CDK4/6-experienced patient sub-population of CAPItello-291, Turner N Engl J Med 2023; 388:2058-2070) ; 1L breast cancer: CDK+ET in 2L+ (PACE Ph2: SABCS 2022 #GS3-06; postMONARCH Ph3: ASCO 2024 #1001; MAINTAIN Ph2: ASCO 2022 #LBA1004); atirmociclib Ph1: Pfizer R&D Oncology Day Feb 2024; vascular anomalies: alpelisib (EPIK-P2, Canaud 2024 Blood 144:5512) and KP-001 (Ozeki 2025, Orphanet Journal of Rare Diseases 20:64); 2. TAM calculated based on market benchmarks and internal analysis; 3. ReDiscover preliminary data as of 01/13/2026 Note: These data are derived from different clinical trials at different points in time, with differences in molecule composition, trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. 2L Breast Cancer 1L Breast Cancer Vascular Anomalies Zovegalisib granted BTD ~$2-3B ~$7-8B ~$6-8B Capi + fulv in 2L: 5.5mo mPFS Alpelisib & KP-001 11-16% VRR at week 12 & 16 CDK + ET in 2L+ 14-32% ORR 11.1mo mPFS at pivotal dose Rapid execution of ongoing 2L pivotal trial 1H 2026 12-wk clinical data to support proof of concept Registrational trial strategy 44% ORR in median 3L patients for Zovega + Atirmo + fulv triplet Aim to initiate 1L pivotal trial in early 2027 US TAM2 Opportunity Anticipated 2026 disclosures key value drivers Zovegalisib Program Hurdle1 Clinical Benchmark ~$555M Cash as of end 4Q 2025 VRR = Volumetric Response Rate ReDiscover preliminary data: doublet at of 01/13/2026, triplet as of 04/13/2026
