UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
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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 7.01 Regulation FD Disclosure.
On December 11, 2024, Relay Therapeutics, Inc. (the "Company") issued a press release announcing updated interim clinical data, as of a November 4, 2024 data cut-off date (the "Data Cut-off Date"), for RLY-2608, the first known allosteric, pan-mutant and isoform-selective inhibitor of phosphoinostide 3 kinase alpha ("PI3Kα"), a copy of which is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K. The Company intends to host a conference call and live webcast to discuss the updated interim clinical data on December 11, 2024 at 7:00 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 December 11, 2024, the Company announced updated interim clinical data for RLY-2608 that were presented at the San Antonio Breast Cancer Symposium 2024.
RLY-2608 is currently being evaluated in the Company's ReDiscover Study, an ongoing first-in-human study, which was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of RLY-2608 in combination with fulvestrant, and in combination with fulvestrant and ribociclib or atirmociclib.
As of the Data Cut-off Date, the RLY-2608 and fulvestrant combination arm of the study had enrolled 118 patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer across all doses in both the dose escalation and dose expansion portions of the study, including 64 patients at the Company’s recommended Phase 2 dose ("RP2D") of 600mg twice daily ("BID"). Among these 64 patients, 31 had a kinase mutation and 33 had a non-kinase mutation. Twelve patients also had a PTEN or AKT co-mutation and were therefore excluded from the efficacy analysis, consistent with the planned pivotal population.
All patients in the RLY-2608 and fulvestrant combination arm across doses had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received the RP2D:
Among the 52 patients in the RLY-2608 and fulvestrant combination arm who received the RP2D and did not have a PTEN or AKT co-mutation:
RLY-2608 in combination with fulvestrant was generally well tolerated in the 118 patients treated across all doses as of the Data Cut-off Date. The overall tolerability profile consisted of mostly low-grade treatment-related adverse events ("TRAEs") that were
manageable and reversible. Safety outcomes were generally as expected across dose levels based on exposure and consistent with mutant-selective PI3Kα inhibition. Among the 64 patients who received the RP2D:
The Company continues to progress two front-line triplet regimens with RLY-2608 and fulvestrant – one with the existing CDK4/6 standard-of-care, ribociclib, and one with Pfizer Inc.'s investigative selective-CDK4 inhibitor, atirmociclib. The RLY-2608, fulvestrant and ribociclib dose escalation is ongoing with biologically active doses of RLY-2608. The RLY-2608, fulvestrant and atirmociclib arm of the ReDiscover study has been initiated.
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; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, as well as the clinical data for RLY-2608; the interactions with regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; the expected strategic benefits under the Company’s clinical trial collaboration with Pfizer; the cash runway projection and the expectations regarding the Company's use of capital and expenses. 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 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; 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 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 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 December 11, 2024, furnished herewith. |
99.2 |
Corporate presentation, dated December 11, 2024, furnished herewith. |
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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.
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RELAY THERAPEUTICS, INC. |
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Date: |
December 11, 2024 |
By: |
/s/ Brian Adams |
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Brian Adams |
Exhibit 99.1
Relay Therapeutics Announces Updated Interim Data for RLY-2608 + Fulvestrant Demonstrating Continued Maturation of Clinically Meaningful Progression Free Survival
New interim data show 11.4-month median PFS in 2L patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer at RP2D
39% confirmed ORR across all patients & 67% in patients with kinase mutations at RP2D
Data support planned initiation of 2L pivotal study in 2025
Next-generation triplet combination with atirmociclib (CDK4-selective) initiated & ribociclib triplet combination ongoing
Relay Therapeutics to host a conference call today, December 11, at 7am ET (6am CT)
San Antonio, Tex. – December 11, 2024 – Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies, today announced updated interim clinical data for RLY-2608, the first known investigational allosteric, pan-mutant and isoform-selective inhibitor of PI3Kα. The updated data show a median progression free survival (PFS) of 11.4 months in second line (2L) patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer who received RLY-2608 600mg twice daily (BID) + fulvestrant. These data are being presented today at the San Antonio Breast Cancer Symposium (SABCS) 2024.
“These updated data help build on previously reported results that show a level of benefit that had not previously been seen with non-selective PI3Kα inhibitors,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “We are particularly encouraged to see even greater benefit observed in the patients in which we are working to start a pivotal study next year; in these 2L patients, RLY-2608 + fulvestrant demonstrated a median progression free survival that is more than twice that of the existing standards-of-care.”
ReDiscover – RLY-2608 First-in-Human Study
RLY-2608 is currently being evaluated in ReDiscover, an ongoing first-in-human study, which was designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of RLY-2608 in combination with fulvestrant, and in combination with fulvestrant and ribociclib or atirmociclib (Pfizer’s selective CDK4 inhibitor).
The RLY-2608 + fulvestrant arm of the study, as of the November 4, 2024 interim data cut-off for this arm, had enrolled 118 patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer across all doses in both the dose escalation and dose expansion portions of the study, including
64 patients at the company’s recommended Phase 2 dose (RP2D) of 600mg BID. Among these 64 patients, 31 had a kinase mutation and 33 had a non-kinase mutation. Twelve patients also had a PTEN or AKT co-mutation and were therefore excluded from the efficacy analysis, consistent with the planned pivotal population.
The RLY-2608 + ribociclib + fulvestrant arm of the study continues to enroll patients with PI3Kα-mutated, HR+, HER2- locally advanced or metastatic breast cancer in dose escalation. The RLY-2608 + atirmociclib + fulvestrant arm of the study has recently been initiated.
Patients were Heavily Pre-Treated
All RLY-2608 + fulvestrant patients across doses had received a significant level of prior therapy in the advanced setting, including at least one prior endocrine therapy and at least one prior CDK4/6 inhibitor. Among the 64 patients who received the RP2D:
Promising Efficacy Data in Proposed Pivotal Population
Among the 52 RLY-2608 + fulvestrant patients who received the RP2D and did not have a PTEN or AKT co-mutation:
Maintained Meaningfully Differentiated Tolerability Profile
RLY-2608 + fulvestrant was generally well tolerated in the 118 patients treated across all doses as of the data cut-off date. The overall tolerability profile consisted of mostly low-grade treatment-related adverse events (TRAEs) that were manageable and reversible. Safety outcomes were generally as expected across dose levels based on exposure and consistent with mutant-selective PI3Kα inhibition. Among the 64 patients who received the RP2D:
Continued Progression of Front-Line Breast Cancer Regimens
Two front-line triplet regimens are being progressed – one with the existing CDK4/6 standard-of-care ribociclib and one with Pfizer’s investigative selective-CDK4 inhibitor atirmociclib. RLY-2608 + ribociclib + fulvestrant dose escalation is ongoing with biologically active doses of RLY-2608. The RLY-2608 + atirmociclib + fulvestrant arm of the ReDiscover study has been initiated.
Anticipated RLY-2608 Next Steps
Cash balance will be operationalized to preserve ability to complete 2L pivotal study
As of the end of the third quarter of 2024, cash, cash equivalents and investments were approximately $840 million.
Conference Call Information
Relay Therapeutics will host a conference call and live webcast today, December 11, 2024, at 7:00 a.m. ET (6:00 a.m. CT). 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.
The data presentation from the San Antonio Breast Cancer Symposium is also available on the Relay Therapeutics website in the “Publications/Presentations” section through the following link: https://relaytx.com/pipeline/.
About RLY-2608
RLY-2608 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, with oncogenic mutations detected in about 14% of patients with solid tumors. RLY-2608 has the potential, if approved, to address more than 300,000 patients per year in the United States, one of the largest patient populations for a precision oncology 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 RLY-2608, 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 RLY-2608. RLY-2608 is currently being evaluated in a first-in-human study designed to treat patients with advanced solid tumors with a PIK3CA (PI3Kα) mutation. For more information on RLY-2608, please visit here.
About Relay Therapeutics
Relay Therapeutics is a clinical-stage precision medicine company transforming the drug discovery process by combining leading-edge computational and experimental technologies with the goal of bringing life-changing therapies to patients. As the first of a new breed of biotech created at the intersection of complementary techniques and technologies, Relay Therapeutics aims to push the boundaries of what’s possible in drug discovery. Its 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. Relay Therapeutics’ initial focus is on enhancing small molecule therapeutic discovery in targeted oncology and genetic disease indications. For more information, please visit www.relaytx.com or follow us on Twitter.
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; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, as well as the clinical data for RLY-2608; the interactions with regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; the
cash runway projection and the expectations regarding Relay Therapeutics’ use of capital and expenses. 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; 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:
Megan Goulart
617-322-0814
mgoulart@relaytx.com
Media:
Dan Budwick
1AB
973-271-6085
dan@1abmedia.com
2024 SABCS – RLY-2608 Data Update December 2024 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 Relay Therapeutics' strategy, business plans and focus; the progress and timing of the clinical development of the programs across Relay Therapeutics' portfolio; the expected therapeutic benefits and potential efficacy and tolerability of RLY-2608, both as a monotherapy and in combination with other agents, and its other programs, including lirafugratinib as well as the clinical data for RLY-2608; the interactions with and approval of regulatory authorities and any related approvals; the potential market opportunity for RLY-2608; and the expected strategic benefits under Relay Therapeutics' clinical trial collaboration with Pfizer; the cash runway projection and the expectations regarding Relay Therapeutics' use of capital and expenses. 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, as well as on 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 or interim 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 and that interim and early clinical data may change as more patient data become available and are subject to audit and verification procedures; 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
Agenda RLY-2608 data presented at 2024 San Antonio Breast Cancer Symposium RLY-2608 – Other Updates 2 ReDiscover Trial Update – RLY-2608 + Fulvestrant Doublet Data Dr. Sammons – overview of evolving treatment landscape Data summary 1 Next steps 3
PI3Kα Mutations Represent a Large Commercial Opportunity PI3Kα mutations represent a large commercial opportunity Non-selective PI3Kα targeting has significant limitations Relay Tx’s Dynamo®️ Platform created mutant selective molecule Breast Cancer Vascular Malformations Non-Breast Cancer Solid Tumors ~140k pts (prevalence¹) ~170k pts (prevalence²) ~90k pts (incidence³) Challenging Tolerability Limited Efficacy RLY-2608 Limited Combinability 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy, excluding PTEN co-mutations (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalent US patient population of vascular malformation patients with a PIK3CA mutation (multiple sources); 3. Incident US patient population solid tumors annually with a PIK3CA mutation, excluding PTEN and KRAS co-mutations (SEER; 3rd party source for alteration rate, May 2024)
Breast Cancer – Large Market for Mutant-Selective PI3Kα Targeted Therapies CDK4/6 + AI (abema / ribo / palbo) 1L Endocrine Sensitive 10,000 pt CDK4/6 + fulvestrant Inavolisib + palbo + fulv Capivasertib + fulvestrant or Alpelisib + fulvestrant or Everolimus + AI Current PI3Kα Pathway Total Addressable Market2 (Metastatic HR+/HER2- Breast Cancer) $6B+ CDK4 + next gen oral ET Oral SERD monoTx Inavolisib + fulv ADCs Emerging TX RLY-2608 combinations Current Standard of Care 1L Endocrine Resistant 6,000 pt 2L Post-CDK4/6 13,000 pt Fulvestrant or elacestrant 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy, excluding PTEN co-mutations (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Relay Tx PIK3CA internal market forecast (patient-based – US, EU5, Japan). Forecast includes estimates for genetic testing, class share, market access, compliance, duration of therapy and assumes current PIK3CA therapy net price (primary sources: SEER; GloboCan; Global Data; Evaluate Pharma; DRG Market Forecast; PIK3CAi PIs) PIK3CA mutated HR+/HER2- BC Treatment Paradigm1
RLY-2608 – Interim Clinical Data Continue to Show Clinically Meaningful PFS 1. CAPItello-291: Turner N Engl J Med 2023; 388:2058-2070; 2. In CAPItello-291, CBR and ORR not reported for CDK4/6-experienced patient population; ORR = objective response rate, mPFS = median progression free survival, LoT = line of therapy (metastatic setting), SoC = Standard of Care, TRAE = treatment related adverse effects, RP2D = recommended Phase 2 dose, CBR = clinical benefit rate, SERD = selective estrogen receptor degrader; Note: data shown are not from head-to-head studies, and no head-to-head studies have been conducted. Favorable Efficacy PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post CDK4/6) Favorable Tolerability 42% Gr3 TRAE Capivasertib + Fulv1 (4 days on, 3 off) 31% Gr3 TRAE RLY-2608 + Fulv (600 mg BID, RP2D) More Heavily Pre-Treated Pt 23% ≥2 prior LoT 0% Prior SERD 41% ≥2 prior LoT 52% Prior SERD Interim RLY-2608 safety and efficacy data supportive of pivotal trial in 2L Breast Cancer against capivasertib Capi ORR & CBR include 30% of pts who are CDK4/6 naïve 5.5mo mPFS 9.2mo mPFS 11.4mo mPFS 9.2mo mPFS ORR: 39% CBR: 67% ORR: 26% CBR: 56% 2L only 2L+ Post-CDK4/6 ReDiscover preliminary data as of 11/04/2024
RLY-2608 – Initial Pivotal Trial Planned for 2L Doublet in 2025* Eligibility Criteria: PIK3CAmut HR+, HER2- advanced / met BC 1 prior line CDK4/6 inhibitor Broad metabolic inclusion criteria No known PTEN or AKT mutation RLY-2608 (600 mg BID, RP2D) + fulvestrant Capivasertib (400 mg BID 4 days on, 3 days off) + fulvestrant R Primary Endpoint: PFS Secondary Endpoints: OS, ORR, DoR, QoL 2L Doublet 2L doublet pivotal start expected in 2025 *Subject to discussions with regulators; eligibility criteria, endpoints, RP2D, and other aspects of trial design have not yet been finalized; OS = overall survival, DoR = duration of response, QoL = quality of life, met BC = metastatic Breast Cancer; 2L = 2nd line
RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Metastatic Breast Cancer 2nd Line Ribociclib triplet and CDK4 triplet ongoing Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Near-Term Focus
Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Ribociclib triplet and CDK4 triplet ongoing RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute
Large Unmet Need in Metastatic Breast Cancer Large unmet need in 2L presents opportunity for well-differentiated targeted agent Ribociclib + AI2 Ribociclib + fulv3 Median PFS of Current Standard of Care 13,000 patients 2L Post-CDK4/6 PIK3CAmut, HR+/HER2- mBC1 6,000 patients 1L Endocrine Resistant 10,000 patients 1L Endocrine Sensitive Notes: 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy, excluding PTEN co-mutations (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. All-comers and PIK3CAmut sub-group, MONALEESA-2; 3. All-comers and PIK3CAmut sub-group, MONALEESA-3; 4. Turner N Engl J Med 2023; 388:2058-2070 (n=355); 5. Rugo 2021 Lancet Oncol 22:489, SABCS 2021 #P1-18-03; 6. MAINTAIN: Kalinsky 2023 J Clin Oncol 41:4004, postMONARCH: Kalinsky 2024 ASCO; 7. Elacestrant Prescribing Information Capivasertib + fulv4 Alpelisib + fulv5 CDK4/6 + fulv6 SERD monotx7 5.5mo 5.6-8mo ~5-6mo ~2-4mo 25 months 16-20 months Inavolisib + palbo + fulv: 15mo 19mo in PIK3CAmut subset analysis Also abemaciclib or palbociclib
RLY-2608 – Mutant-Selective PI3Kα Additive to Many Potential Combinations PI3Kα Backbone Current Standard of Care Non-Mutant Selective Inhibitors (capivasertib, alpelisib, inavolisib) Emerging Options for Future Standard of Care RLY-2608 PIK3CAmut HR+/HER2- Breast Cancer Treatment Paradigm + Cell Cycle Hormone Therapy CDK4/6: Ribociclib, abemaciclib, palbociclib AI / fulvestrant CDK4, CDK2, CDK2/4 Oral SERD/SERM +
RLY-2608 – ReDiscover Trial Overview 1. Excludes PIK3CAmut clear cell OvCA, HNSCC, Cervical cancer, and colorectal patients; 2. Double mutation defined as one major PIK3CA mutation (E542X, E545X, H1047X) + ≥1 additional PIK3CA mutation per local assessment; CCOC = clear cell ovarian cancer Part 2 – Dose Expansion Study Arm Part 1 – Dose Escalation MTD/RP2D PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post-CDK4/6) PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer Focus of Following Data Doublet MTD/RP2D PIK3CAmut Advanced Solid Tumors (CCOC, HNSCC, cervical, other1, double PIK3CA mutants2) PIK3CAmut Advanced Solid Tumors (mixed histologies) Mono MTD/RP2D PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer (post-CDK4/6) PIK3CAmut, HR+/HER2- Advanced / Metastatic Breast Cancer Ribociclib (CDK4/6) Atirmociclib (CDK4) MTD/RP2D Triplet RLY-2608 + Fulvestrant RLY-2608 RLY-2608 + Fulvestrant + CDK4/6 & CDK4i
RLY-2608 – ReDiscover Trial Enrollment Part 2 – Dose Expansion RLY-2608 + Fulvestrant Doublet 200 mg BID – N=3 100 mg BID – N=3 800 mg BID – N=16 1000 mg BID – N=1 600 mg BID – N=17 600 mg BID – N=47 Study Arm Part 1 – Dose Escalation 64 patients total across dose escalation and expansion at 600 mg BID 400 mg BID – N=10 400 mg BID1 – N=21 Safety Database – 118 patients across all doses Efficacy Database at 600mg BID – 52 patients (excludes 12 PTEN / AKT co-mutation patients2) 1. 400mg cohort is not yet mature for efficacy analysis. Full Phase I results, including 400mg cohort, will be disclosed at a later date; 2. As defined by central ctDNA RP2D ReDiscover preliminary data as of 11/04/2024
RLY-2608 – ReDiscover Trial Baseline Demographics ReDiscover preliminary data as of 11/04/2024 RLY-2608 + Fulvestrant All Patients (N=118) 600 mg BID (RP2D, N=64) Age, Median (Range), Years 59.0 (34, 85) 59.0 (34, 80) ECOG, 0 / 1, n (%) 69 (58.5) / 49 (41.5) 38 (59.4) / 26 (40.6) Local PIK3CA Baseline Results Kinase Mutation, n (%) 57 (48.3) 31 (48.4) Non-Kinase Mutations, n (%) 61 (51.7) 33 (51.6) BMI >30 or HbA1c >5.7%, n (%) 44 (37.3) 22 (34.4) Measurable Disease, n (%) 83 (70.3) 42 (65.6) Patients with Visceral Metastases, n (%)1 75 (63.6) 38 (59.4) Prior Lines of Therapy in Advanced Setting 1, n (%) 62 (52.5) 38 (59.4) 2+, n (%) 56 (47.5) 26 (40.6) Prior Therapies in Advanced Setting CDK4/6, n (%)2 118 (100.0) 64 (100.0) Fulvestrant or Novel SERD, n (%) 66 (55.9) 33 (51.6) Chemo / ADC, n (%) 30 (25.4) 16 (25.0) ESR1 Mutation (Central Read)3, n (%) 40 (35.4) 18 (28.6) 1. Visceral metastatic sites include brain, lung, liver, pleural, peritoneal involvement; 2. Three patients received prior CDK4/6 in the adjuvant setting which is allowed per protocol; 3. Percentage was based on pts with evaluable ctDNA data at baseline; ECOG = Eastern Cooperative Oncology Group performance status
RLY-2608 – Efficacy: Median PFS 9.2 Months in All Patients & 11.4 Months in 2L ReDiscover preliminary data as of 11/04/2024 Note: Follow-up estimated based on reversed KM. PFS estimates based on KM methods. Time Since First Dose (months) RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations Progression-Free Survival (%) 2L Patients (N=32) All Patients (N=52) 6-month PFS: 66.3% 9-month PFS: 63.2% CBR: 32/48 (66.7%) Median follow-up: 9.5mo 9.2mo mPFS (95% CI: 5.8, 18.4) 6-month PFS: 78.9% 9-months PFS: 72.3% CBR: 21/ 30 (70.0%) Median follow-up: 7.4mo 11.4mo mPFS (95% CI: 7.2, NR) Time Since First Dose (months) Progression-Free Survival (%) Number of Patients at Risk: Number of Patients at Risk:
PR RLY-2608 – Efficacy: Confirmed ORR 39% ReDiscover preliminary data as of 11/04/2024 RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT Co-Mutations – Measurable Disease (N=31) ORR: 12/31 (38.7%) (95% CI: 21.8%, 57.8%) Tumor Reduction: 23/31 (74.2%) PIK3CA mutation: “K” = Kinase domain mutation, “NK” = Non-Kinase domain mutation; CR = Complete Response Not shown: CR in pt with non-measurable disease SD PD BOR = Best Overall Response: Stable Disease Progressive Disease Partial Response
RLY-2608 – Efficacy: ctDNA Clearance PIK3CA ctDNA Variant Allele Frequency (%) Kinase Non-Kinase 1. N=36 patients without PTEN/AKT co-alterations who have detectable PIK3CA at baseline and a paired C1D1-C2D1 ctDNA result are presented RLY-2608 (600 mg BID) + Fulvestrant (N=36) RLY-2608 (All Doses) + Fulvestrant (N=70) ReDiscover preliminary data as of 11/04/2024 At 600 mg BID1 (RP2D): 35 (97.2%) patients had decline in PIK3CA ctDNA 19 (52.8%) patients completely cleared PIK3CA ctDNA by C2D1
RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT co-mutations (N=29) 11.4 mo mPFS (95% CI: 9.2, NR) RLY-2608 600 mg BID (RP2D) + Fulvestrant Excluding PTEN / AKT – Measurable Disease (N=15) 66.7% ORR (10/15 pt, 95% CI: 38.4%, 88.2%) Not shown: CR in pt with non-measurable disease RLY-2608 – Efficacy: Kinase Mutations mPFS 11.4 Months & Confirmed ORR 67% ReDiscover preliminary data as of 11/04/2024 PR SD PD BOR = Best Overall Response: Stable Disease Progressive Disease Partial Response
RLY-2608 – Tolerability: Limited Observed Impact on Glucose Homeostasis ReDiscover preliminary data as of 11/04/2024 Alpelisib Label Criteria* 100 mg BID (N=3) 200 mg BID (N=3) 400 mg BID (N=31) 600 mg BID (N=64) 800 mg BID (N=16) 1000 mg BID (N=1) Glucose (mg/dL) RLY-2608 + Fulvestrant Grade 3 (250-500 mg/dL) Grade 2 (160-250 mg/dL) Grade 1 (115-160 mg/dL) Note: *Based on CTCAE version 4 criteria
All Patients (N=118) 600mg BID (RP2D, N=64) All Gr Gr3 All Gr Gr3 Any TRAE 92.4% 25.4% 93.8% 31.3% TRAEs ≥15% of 600 mg BID Hyperglycemia1 42.4% 2.5% 46.9% 3.1% Nausea 41.5% 0.8% 50.0% 1.6% Fatigue1 40.7% 8.5% 35.9% 9.4% Creatinine Increased 34.7% 0.8% 34.4% 1.6% Diarrhea 30.5% 1.7% 35.9% 3.1% Decreased Appetite 16.9% 0% 20.3% 0% Headache 15.3% 0.8% 20.3% 0% Hypokalaemia1 15.3% 1.7% 17.2% 1.6% Vomiting 12.7% 0% 15.6% 0% Other select TRAEs Rash1 11.9% 0.8% 10.9% 1.6% Stomatitis 3.4% 0.8% 4.7% 0% RLY-2608 – Tolerability: TRAEs ReDiscover preliminary data as of 11/04/2024 No Gr4-5 TRAEs 1: Hyperglycemia includes the MedDRA v26.0 Preferred Terms (PT): Hyperglycemia, Blood Glucose Increased, Glucose Tolerance Impaired; Fatigue includes the PTs: Fatigue, Asthenia; Hypokalemia includes the PTs: Hypokalemia and blood potassium decreased; Rash includes the PTs: Rash, Rash Macular, Rash Maculo-Papular 27% Gr1 hyperglycemia (no intervention required)
Note: 1. Fatigue includes the PTs: Fatigue and Asthenia; TRAEs leading to Dose Reduction in more than 2 patients within 600 mg BID are presented. RLY-2608 – Tolerability: Dose Intensity and Modifications Maintained 94% dose intensity with very low TRAE discontinuations at 600mg BID All Patients (N=118) 600mg BID (RP2D, N=64) Dose Intensity Relative Dose Intensity (%), Median 97% 94% Dose Modifications Due to TRAE Dose Reduction, n (%) 38 (32.2) 25 (39.1) Dose Interruption, n (%) 56 (47.5) 33 (51.6) Dose Discontinuation, n (%) 7 (5.9) 2 (3.1) TRAEs Leading to Dose Reduction Fatigue1 12 (10.2) 6 (9.4) Blood Creatinine Increased 8 (6.8) 3 (4.7) Diarrhea 6 (5.1) 3 (4.7) Grade 1 pruritis; Grade 1 nausea and loss of appetite ReDiscover preliminary data as of 11/04/2024
1. SABCS 2021 #P5-17-05 (n=60); 2. SABCS 2021 #PD-13-05; 3. Turner N Engl J Med 2023; 388:2058-2070 (n=355); 4. 5.5mo mPFS reported in CDK4/6-experienced patient sub-population of CAPItello-291; 5. Prior SERD includes fulvestrant and next-generation SERDs; 6. FDA Prescribing Information. 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. 24% 37% ORR CBR 26%6 56% 19% 48% Capi ORR & CBR include 30% of pts who are CDK4/6-naïve 7.1mo 5.6mo 5.5mo 5.5mo4 mPFS 39% 67% 9.2mo 33% 0% 47% 52% 63% 23% 57% 39% % prior SERD5 % pt with >=2 prior LoT Data Benchmark BYLieve Cohort C2 (N=126) CAPItello-2913,6 (N=355) Ph1b Arm D1 (N=60) ReDiscover (N=52) Doublet Combination Regimens Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) not approved approved 2019 approved 2023 ReDiscover preliminary data as of 11/04/2024 PI3Kα Inhibitors – Efficacy Profiles
RLY-2608 – Monotherapy Activity in Breast Cancer ORR: 1/3 (33%) DCR: 2/3 (67%) RLY-2608 Active as Monotherapy All HR+/HER2- Breast Cancer Patients Across All Doses (N=3)* No endometrial patients dosed* Relay Tx Focus on Significant Commercial Opportunities 2L Breast Cancer 13,000 pt Vascular Malformations 170,000 pt 10,000 pt Endocrine Sensitive Endocrine Resistant 6,000 pt BC combinations & VMs are near-term development focus; other solid tumor development currently deprioritized 1L Breast Cancer * Within efficacy evaluable population, which excludes PTEN co-mutated patients Treatment (mg) # prior lines PIK3CAmut BOR 0 -70 -60 -50 -40 -30 -20 -10 200mg QD 400mg QD 400mg BID 6 5 12 K K K SD PD PR 0 10 20 30 40 50 Best % change from baseline (RECISTv1.1) ReDiscover preliminary data as of 11/18/2024
RLY-2608 – Initial Pivotal Trial Planned for 2L Doublet in 2025* Eligibility Criteria: PIK3CAmut HR+, HER2- advanced / met BC 1 prior line CDK4/6 inhibitor Broad metabolic inclusion criteria No known PTEN or AKT mutation RLY-2608 (600 mg BID, RP2D) + fulvestrant Capivasertib (400 mg BID 4 days on, 3 days off) + fulvestrant R Primary Endpoint: PFS Secondary Endpoints: OS, ORR, DoR, QoL 2L Doublet 2L doublet pivotal start expected in 2025 *Subject to discussions with regulators; eligibility criteria, endpoints, RP2D, and other aspects of trial design have not yet been finalized; OS = overall survival, DoR = duration of response, QoL = quality of life, met BC = metastatic Breast Cancer; 2L = 2nd line
Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Ribociclib triplet and CDK4 triplet ongoing
RLY-2608 – On Track to Realize 1L Potential with Triplet Combinations Phase 1 Aim for Triplets: Demonstrate safety, tolerability and preliminary efficacy with both current generation CDK4/6 and next-gen CDK4 to enable pivotal development potential in both Atirmociclib triplet has initiated Currently dosing at biologically active doses of RLY-2608 Dose Escalation RLY-2608 Fulvestrant + Ribociclib (CDK4/6, commercial SoC) Atirmociclib (CDK4, Pfizer) + + RLY-2608 Fulvestrant + Triplets
2L doublet pivotal start expected in 2025 Ribociclib triplet and CDK4 triplet ongoing RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Metastatic Breast Cancer 2nd Line Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Clinical start expected in 1Q 2025
Vascular Malformations – Over 170,000 US Patients US Patients % PIK3CAmut Approved Therapies Lymphatic Malformation (LM) Venous Malformation (VM) Cerebral Cavernous Malformation (CCM) PIK3CA-Related Overgrowth Spectrum (PROS) ~80k 80% ~65k pt ~100k ~20-25% ~20-25k pt ~120k 40-55% ~50-65k pt ~5-15k 100% ~5-15k pt No approved systemic therapy Vijoice® (alpelisib) Total US pt across types >300k pt ~170k pt PIK3CAmut Sources: ISSVA classification, NORD, Mayo Clinic, Novartis, Penington et al 2023, Gallagher et al 2022, Luks et al 2015, Limaye et al 2015, Peyre et al 2021, Hong et al 2021. Photo sources: Venot et al. Nature 2018, Wenger et al Genet Med 2022, Limaye et al Nature Genetics 2008, Mayo Clinic Vascular Malformation Types
Vascular Malformations – Proposed Study Design PIK3CAmut Vascular Malformation (VM) Patients (PROS & Other PIK3CA VMs) Adults & Adolescents (≥12 years old) Pediatrics (6-12 years old) Pediatrics (2-6 years old) Part 1: Dose Selection RP2D(s) Part 2: Dose Expansion Expansion Cohort(s) Expansion Cohort(s) Expansion Cohort(s) Dose Escalation Dose Escalation RP2D(s) RP2D(s) Group Randomized Dose Finding
RLY-2608 – Multiple Mutant-Selective PI3Kα Opportunities Clinical start expected in 1Q 2025 2L doublet pivotal start expected in 2025 Metastatic Breast Cancer 2nd Line Ribociclib triplet and CDK4 triplet ongoing Metastatic Breast Cancer 1st Line Vascular Malformations PI3Kα Franchise Team and Capital to Execute Near-Term Focus
PI3Kα Inhibitors – Tolerability Profiles 1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information; 4. 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. Grade 3+ Hyperglycemia All Grade 3+ TRAEs Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) Doublet Combination Regimens Dose Discontinuation due TRAEs not approved approved 2019 approved 2023 Discontinuous dosing: 4 days on, 3 days off Ph1b Arm D1 (n=60) BYLieve2 (n=127) FDA Label3 (n=355) Data Benchmark ReDiscover (n=64) 0% 42%4 34% of pt BMI ≥30 and/or HbA1c ≥5.7% ReDiscover preliminary data as of 11/04/2024
1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489; 3. FDA Prescribing Information; 4. per CAPItello-291 enrollment criteria; 5. Rash for capivasertib references Cutaneous Adverse Reactions grouped term includes a number of preferred terms listed in FDA Prescribing Information. 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. Diarrhea Rash5 Hyperglycemia Ph1b Arm D1 (n=60) BYLieve2 (n=127) FDA Label3 (n=355) Data Benchmark ReDiscover (n=64) <7% ≤6.4% <8%4 HbA1c Enrollment Criteria <7% Gr1-2 Gr3+ Gr1 Gr2 Stomatitis 34% of pt BMI ≥30 and/or HbA1c ≥5.7% Doublet Combination Regimens Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) not approved approved 2019 approved 2023 62% 6% 10% 3% 59% 60% 29% 31% 2% 12% 15% 2% 19% 77% 56% 25% 3% 3% 2% 47% 36% 11% ReDiscover preliminary data as of 11/04/2024 PI3Kα Inhibitors – Tolerability Profiles
PI3Kα Inhibitors – Efficacy Profiles 1. SABCS 2021 #P5-17-05 (n=60); 2. SABCS 2021 #PD-13-05; 3. Turner N Engl J Med 2023; 388:2058-2070 (n=355); 4. 5.5mo mPFS reported in CDK4/6-experienced patient sub-population of CAPItello-291; 5. Prior SERD includes fulvestrant and next-generation SERDs; 6. FDA Prescribing Information. 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. 24% 37% ORR CBR 26%6 56% 19% 48% Capi ORR & CBR include 30% of pts who are CDK4/6-naïve 7.1mo 5.6mo 5.5mo 5.5mo4 mPFS 39% 67% 9.2mo 33% 0% 47% 52% 63% 23% 57% 39% % prior SERD5 % pt with >=2 prior LoT Data Benchmark BYLieve Cohort C2 (N=126) CAPItello-2913,6 (N=355) Ph1b Arm D1 (N=60) ReDiscover (N=52) Doublet Combination Regimens Alpelisib + fulvestrant Capivasertib + fulvestrant Inavolisib + fulvestrant RLY-2608 + fulvestrant (600mg BID, RP2D) not approved approved 2019 approved 2023 ReDiscover preliminary data as of 11/04/2024
Large Unmet Need in Metastatic Breast Cancer 13,000 patients 2L Post-CDK4/6 PIK3CAmut, HR+/HER2- mBC1 6,000 patients 1L Endocrine Resistant 10,000 patients 1L Endocrine Sensitive Notes: 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy, excluding PTEN co-mutations (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. All-comers and PIK3CAmut sub-group, MONALEESA-2; 3. All-comers and PIK3CAmut sub-group, MONALEESA-3; 4. Turner N Engl J Med 2023; 388:2058-2070 (n=355); 5. Rugo 2021 Lancet Oncol 22:489, SABCS 2021 #P1-18-03; 6. MAINTAIN: Kalinsky 2023 J Clin Oncol 41:4004, postMONARCH: Kalinsky 2024 ASCO; 7. Elacestrant Prescribing Information; 8. Informed by qualitative and quantitative primary market research performed in Q2 2024 Capivasertib + fulv4 Alpelisib + fulv5 CDK4/6 + fulv6 SERD monotx7 Ribociclib + AI2 Ribociclib + fulv3 Median PFS of Current Standard of Care 5.5mo 5.6-8mo ~5-6mo ~2-4mo 25 months 16-20 months Current Market Oppty Future Market Oppty Potential Market Opportunity8 ~$6-7B ~$4B ~$2B ~$3-4B ~$2B ~$3-4B RLY-2608 Potential to Drive Meaningful Improvement Also abemaciclib or palbociclib
Relay Tx – Additional Near-Term Clinical Programs 1. Prevalence of Fabry patients, 2025 (National Fabry Disease Foundation, Nov 2024); 2. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024); 3. Fabry disease forecasted 2024 market size per EvaluatePharma, includes Galafold® and ERTs (May 2024) Solid Tumors NRAS-Driven Solid tumors Clinical start in 2H 2025 ~28,000 pts2 1st NRAS-selective inhibitor Fabry Disease Clinical start in 2H 2025 ~8,000 pts1 (chronic treatment) 1st non-inhibitory αGal chaperone GENETIC DISEASE $2B current market3 Anticipated Milestones Large US Opportunity Program Updates
Relay Tx – Broad Precision Medicine Pipeline Target Program Preclinical Early Clinical Late Clinical BREAST CANCER PI3Kα RLY-2608 (PI3KαPAN) Endocrine Tx (ET) doublet Ribociclib + ET triplet CDK4i + ET triplet Other Novel Combinations CDK2 RLY-2139 ERα RLY-1013 (Degrader) GENETIC DISEASE Fabry Disease αGal Chaperone Vascular Malformations RLY-2608 (PI3KαPAN) Other PI3KαPAN SOLID TUMORS NRAS NRAS-selective Inhibitor PI3Kα RLY-2608 FGFR2 Lirafugratinib (RLY-4008) Paused; IND ready Advance to IND-ready Global Outlicense to Elevar Therapeutics Dynamo®️ Platform 5 unnamed research programs
Significant Capital to Achieve Goals Relay Tx – Capital, Team & Execution Focus to Deliver on Milestones Cash as of the end of 3Q 2024 ~$840M Expected to fund current operating plan into 2H 2027 Anticipated 2025 Corporate Objectives 2L pivotal trial start – 2025 Full Ph1-2 data – 2025 Breast Cancer RLY-2608 Vascular Malformations RLY-2608 Fabry Disease Pre-clinical NRAS Pre-clinical Clinical start – 1Q 2025 Clinical start – 2H 2025 Clinical start – 2H 2025 Dynamo®️ Platform 5 unnamed research programs
RLY-2608 – Efficacy: CBR 67% ReDiscover preliminary data as of 11/04/2024 RLY-2608 600 mg BID + Fulvestrant Excluding PTEN / AKT Co-Mutations (N=52) CBR: 32/48 (66.7%)