UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
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 June 5, 2024, Relay Therapeutics, Inc. (the “Company”) issued a press release announcing a clinical trial collaboration between the Company and Pfizer, Inc. (“Pfizer”), a copy of which is furnished herewith as Exhibit 99.1.
On June 6, 2024, the Company issued a press release announcing three new programs from its existing pre-clinical pipeline, a copy of which is being furnished as Exhibit 99.2 to this Current Report on Form 8-K. The Company intends to host a New Program and Platform event on June 6, 2024 from 8:00 to 10:00 a.m. ET to discuss these new programs and describe how the Dynamo™ platform led to these discoveries. The Company has made available a slide presentation to accompany this event, a copy of which is being furnished as Exhibit 99.3 to this Current Report on Form 8-K.
The information in this Item 7.01, including Exhibit 99.1, Exhibit 99.2 and Exhibit 99.3 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 June 5, 2024, the Company announced a global clinical trial collaboration with Pfizer for the development of RLY-2608 in combination with fulvestrant and atirmociclib, Pfizer's investigative selective-CDK4 inhibitor, in patients with PI3Kα-mutated, HR+, HER2- metastatic breast cancer. On June 6, 2024, the Company announced three new programs from its existing pre-clinical pipeline, including two novel programs from its genetic disease portfolio to address clinically and commercially validated targets in vascular malformations and Fabry disease, respectively, and an NRAS-selective inhibitor.
Cautionary Note Regarding Forward Looking Statements
This Current Report on Form 8-K and certain of the 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 updates on the clinical development of the programs across the Company’s portfolio, including the expected therapeutic benefits of its programs, and potential efficacy and tolerability, and the timing and success of interactions with and approval of regulatory authorities; the timing of clinical data updates across the Company’s pipeline, including the progress of doublet and triplet combinations for RLY-2608, the timing of clinical updates for RLY-2608, and the timing of a clinical data and regulatory update for lirafugratinib; the timing of clinical initiation of the Company’s various programs, including a potential pivotal trial for RLY-2608, clinical development in vascular malformations, clinical development of the Company’s non-inhibitory chaperone, and clinical development of its NRAS-selective inhibitor; the potential of the Company’s product candidates to address a major unmet medical need; the cash runway projection; the competitive landscape and potential market opportunities for the Company’s product candidates; the expected strategic benefits under the Company’s collaborations, including the clinical trial collaboration with Pfizer; the capabilities and development of the Dynamo platform, including its role in identifying product candidates; the Company’s ability to successfully establish or maintain collaborations or strategic relationships for its product candidates; expectations regarding current and future interactions with the U.S. Food and Drug Administration, or FDA; the Company’s ability to manufacture its product candidates in conformity with the FDA’s requirements; plans to develop, manufacture and commercialize the current product candidates and any future product candidates; and the implementation of the Company’s business model and strategic plans for its 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 are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements 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 Current Report on Form 8-K or the materials furnished or filed herewith, including, without limitation, risks associated with: the impact of global economic uncertainty, geopolitical instability, 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 of any current or planned clinical trials or the development of the Company's drug candidates; the risk that the preliminary 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; 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 June 5, 2024, furnished herewith. |
99.2 |
Press release issued by Relay Therapeutics, Inc. on June 6, 2024, furnished herewith. |
99.3 |
New Program and Platform event presentation, dated June 2024, 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: |
June 6, 2024 |
By: |
/s/ Brian Adams |
|
|
|
Brian Adams |
Exhibit 99.1
Relay Therapeutics Announces Clinical Trial Collaboration with Pfizer to Evaluate Atirmociclib in Combination with RLY-2608
Initial triplet combination of RLY-2608 + atirmociclib + fulvestrant to be evaluated in patients with PI3Kα-mutated HR+/HER2- metastatic breast cancer; initiation planned by end of 2024
Cambridge, Mass. – June 5, 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 a clinical trial collaboration with Pfizer Inc. (NYSE: PFE) to evaluate atirmociclib, Pfizer’s investigative selective-CDK4 inhibitor, in combination with RLY-2608 and fulvestrant in patients with PI3Kα-mutated, HR+, HER2- metastatic breast cancer.
“We are very enthusiastic to evaluate Pfizer’s novel investigative selective-CDK4 inhibitor atirmociclib in combination with RLY-2608, the first mutant selective PI3Kα inhibitor,” said Don Bergstrom, M.D., Ph.D., President of R&D at Relay Therapeutics. “We believe that combining these two selective agents – atirmociclib and RLY-2608 – will avoid key off-target toxicity that comes from hitting CDK6 and wild-type PI3Kα, which has historically significantly limited use of non-selective agents. The breast cancer treatment landscape continues to evolve quickly, and we are pleased that the safety profile RLY-2608 has demonstrated to-date makes it well-positioned to be part of the next generation of therapies.”
Under the terms of the agreement, Pfizer will provide atirmociclib for use in the study and Relay will be responsible for conducting the study. The RLY-2608 + atirmociclib + fulvestrant triplet combination is planned to begin by the end of 2024.
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 250,000 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 trial 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, including the timing of clinical initiation of the RLY-2608 + atirmociclib + fulvestrant triplet combination; 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; the potential market opportunity for RLY-2608; and the expected strategic benefits under Relay Therapeutics’ clinical trial collaboration 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 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, 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 of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary 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; 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.
2
Contact:
Megan Goulart
617-545-5526
mgoulart@relaytx.com
Media:
Dan Budwick
1AB
973-271-6085
dan@1abmedia.com
3
Exhibit 99.2
Relay Therapeutics Discloses Three New Programs at New Program & Platform Event
3 new programs include 2 genetic disease programs – vascular malformations & Fabry disease – & 1 precision oncology program – NRAS-specific inhibitor
Cash guidance remains unchanged, and is expected to fund operations into second half of 2026
Relay Therapeutics to host webcast event today, June 6, at 8:00 a.m. ET
Cambridge, Mass. – June 6, 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, will provide details on the company’s portfolio during its New Program & Platform event today, June 6, 2024, from 8:00 to 10:00 a.m. ET. As part of the event, the company will disclose three new programs from its existing pre-clinical pipeline and will review how the Dynamo™ platform led to these discoveries. The new programs include two novel programs from its genetic disease portfolio and a potentially first-in-class NRAS-selective inhibitor. Both genetic disease programs have the potential to provide a unique approach to addressing clinically and commercially validated targets in vascular malformations and Fabry disease. The new programs announced today do not change cash guidance, which is expected to fund operations into the second half of 2026.
“Since Relay Therapeutics was founded eight years ago, our Dynamo platform has been very productive and we have made significant progress advancing our initial set of programs, including four that have entered the clinic. We have successfully created molecules for a variety of targets to-date, have shown clinical proof-of-concept for two of these programs and are aiming to start our first Phase 3 study next year with RLY-2608,” said Sanjiv Patel, M.D., President and Chief Executive Officer of Relay Therapeutics. “Today, we are very excited to unveil the next set of innovative programs, which demonstrate the power of our Dynamo platform, and which we believe will drive the next wave of the company’s growth. These new programs underscore the breadth of the platform’s capabilities with expansion beyond precision oncology into genetic disease and beyond inhibitors to small molecule chaperones.”
New Programs Potentially Addressing More Than 200,000 Patients in the United States
The New Program & Platform event presentation will highlight newly disclosed programs in vascular malformations, Fabry disease and NRAS.
Vascular Malformations
Fabry Disease
NRAS
2
Anticipated Milestones
Platform Productivity
Since the founding of Relay Therapeutics in 2016, the company has built and grown its Dynamo drug discovery platform, which combines experimental and computational techniques, tools and team members. Over the last eight years, Dynamo has been very productive, resulting in eight drug candidates (DCs) and four Investigational New Drug Applications (INDs), including two programs that have demonstrated clinical proof-of-concept. By the end of 2025, Relay Therapeutics expects three new clinical starts from the additional novel programs announced today. Collectively, over the first decade of the company’s history, that would be 11 DCs, seven INDs and seven programs that have entered the clinic.
Cash Runway
The three new programs disclosed today are from Relay Therapeutics’ existing pre-clinical pipeline. The continued advancement of these programs has already been accounted for in the company’s existing cash runway guidance. As of March 31, 2024, cash, cash equivalents and investments totaled approximately $750 million and are expected to fund the current operating plan into the second half of 2026.
3
Event Information
Relay Therapeutics’ New Program & Platform event will begin at 8:00 a.m. ET and is expected to conclude at approximately 10:00 a.m. ET. The live webcast can be accessed here or on 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. It is recommended that participants register at least 15 minutes in advance of the event.
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 updates on the clinical development of the programs across Relay Therapeutics’ portfolio, including the expected therapeutic benefits of its programs, and potential efficacy and tolerability, and the timing and success of interactions with and approval of regulatory authorities; the timing of clinical data updates across Relay Therapeutics’ pipeline, including the progress of doublet and triplet combinations for RLY-2608, the timing of clinical updates for RLY-2608, and the timing of a clinical data and regulatory update for lirafugratinib; the timing of clinical initiation of Relay Therapeutics’ various programs, including a potential pivotal trial for RLY-2608, clinical development in vascular malformations, clinical development of Relay Therapeutics’ non-inhibitory chaperone, and clinical development of its NRAS-selective inhibitor; the potential of Relay Therapeutics’ product candidates to address a major unmet medical need; the cash runway projection; the competitive landscape and potential market opportunities for Relay Therapeutics’ product candidates; the expected strategic benefits under Relay Therapeutics’ collaborations; the capabilities and development of the Dynamo platform, including its role in identifying product candidates; Relay Therapeutics’ ability to successfully establish or maintain collaborations or strategic relationships for its product candidates; expectations regarding current and future interactions with the U.S. Food and Drug Administration (FDA); Relay Therapeutics’ ability to manufacture its product candidates in conformity with the FDA’s requirements; plans to develop, manufacture and commercialize the current product candidates and any future product candidates; and the implementation of Relay Therapeutics’ business model and strategic plans for its 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 are intended to
4
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, 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 of any current or planned clinical trials or the development of Relay Therapeutics’ drug candidates; the risk that the preliminary 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; 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
617-545-5526
mgoulart@relaytx.com
Media:
Dan Budwick
1AB
973-271-6085
dan@1abmedia.com
5
New Program & Platform Event June 2024 Exhibit 99.3
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 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 RLY-2608, the timing of clinical updates for RLY-2608, and the timing of a clinical data and regulatory update for lirafugratinib; the timing of clinical initiation of our various programs, including a potential pivotal trial for RLY-2608, clinical development in vascular malformations, 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 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); our ability to manufacture our product candidates in conformity with the FDA’s requirements; the capabilities and development of our DynamoTM 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, 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 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.
Solid Tumors BREAST CANCER Relay Tx – Today’s Updates NRAS-Driven Solid tumors PI3Kα-Driven Breast Cancer 1 CDK4i clinical start by YE 2024 Clinical start in 2H 2025 ~150,000 pts1 ~28,000 pts4 1st PI3Kαi + ET + CDK4i combination in clinic 1st NRAS-selective inhibitor PI3Kα-Driven Vascular Malformations 2 Clinical start in 1Q 2025 ~170,000 pts2 (chronic treatment) 1st mutant-selective PI3Kα inhibitor Fabry Disease 3 4 Clinical start in 2H 2025 ~8,000 pts3 (chronic treatment) 1st non-inhibitory αGal chaperone GENETIC DISEASE 1. Prevalent US patient population with a PIK3CA mutation in adjuvant, first line metastatic and second line metastatic settings (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalence of vascular malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources); 3. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 4. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024); 5. Fabry disease forecasted 2024 market size per EvaluatePharma, includes Galafold® and ERTs (May 2024) Milestones Large US opportunity Program Updates Ongoing mono, doublet, triplet; Data update YE24 $2B current market5
PI3Kα – Large Opportunity Across Indications and Therapeutic Areas PIK3CA mutant HR+/HER2- Breast Cancer PIK3CA mutant Vascular Malformations PIK3CA mutant Other Solid Tumors Cerebral Cavernous Lymphatic Venous PROS 65k pt 65k pt 25k pt 15k pt ~150k Patients (US prevalence)1 ~170k Patients (US prevalence)2 Colorectal Endometrial Bladder Prostate NSCLC HNSCC 28k pt 20k pt 17k pt 16k pt 14k pt 9k pt Relay Tx's PI3Kα Franchise has the potential to address wide range of large disease indications Adjuvant 1st Line 2nd Line 120k pt 18k pt 14k pt ~160k Patients (US incidence)3 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (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 (SEER; 3rd party source for alteration rate, May 2024) RLY-2608 RLY-2608 Potential for rapid POC with RLY-2608, then distinct molecule for pivotal
Relay Tx – Productive Platform PEOPLE EXPERIMENTATION COMPUTATION PEOPLE Expected platform production by YE 2025 DCs 8 INDs 4 Clinical POC 2 Productive Platform Continued platform Productivity New clinical starts New DCs +3 New INDs +3 +3 ~$750M Cash as of end Q1 2024 Expected to fund current operating plan into 2H 2026 2016 2024 FUTURE EXPECTATIONS Internalize, integrate & expand platform Genetic Disease New Modalities: Chaperones Built computationally enabled platform Solid Tumors Small Molecule Inhibitors & Degraders
2024 Dynamo™ Platform Relay Tx’s Dynamo™ – Productive Computationally Enabled Platform Free energy calculations Digitally encoded libraries Long time-scale MD Differential dynamics Automated Chemical Design Generative design Active learning ADME/PK models ML-DEL + AI models for DEL Giga-scale virtual screening Computational fragment merging COMPUTATION NMR X-ray fragment screening HDX-MS Mechanistic enzymology Cryo-EM REL-DEL Integrated pharmacology Protein design and engineering Ambient temp. X-Ray crystallography Automated Ligand ID System (ALIS) Structure ensembles EXPERIMENTATION Exp. Comp. 2016 PEOPLE High throughput automated chemistry
Focus of the Dynamo™ Platform Experimentation Develop novel modulation hypotheses Rapidly generate multiple lead compounds Optimize lead compounds swiftly and cost-effectively Development & Commercial Target Identification Target Modulation Hypothesis Hit Identification Lead Optimization Computation Relay Tx’s Dynamo™ Platform – Experimentation Closely Integrated with Computation
Dynamo™ Platform Enabled Rapid Creation of First Selective NRAS Inhibitor Compounds evaluated computationally In Vivo PoC 29 compounds synthesized in the lab 1st compound synthesized achieved potent NRAS inhibition 120 days
Outputs Relay Tx’s Dynamo™ – Focused on Output RLY-2608 RLY-5836 RLY-2139 RLY-1013 Migoprotafib Lirafugratinib COMPUTATION PEOPLE EXPERIMENTATION + Multiple unnamed earlier stage research programs Dynamo™ Platform
Relay Tx – Consistent Focus on Validated, Low Translational Risk Programs Breast Cancer Solid Tumors Genetic Disease Productive Dynamo™ Research Engine αGal (Fabry Disease) PI3Kα (Vascular Malformations) Multiple unnamed research stage programs New Programs Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Amenable to Dynamo™️ Platform Target Selection Focus PI3Kα CDK2 ERα NRAS PI3Kα FGFR2 SHP2
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 Monotherapy FGFR2 Lirafugratinib (RLY-4008) SHP2 Migoprotafib (GDC-1971) Paused; IND ready Advance to IND-ready 3 ongoing combo studies (GNE) CDK4i triplet to initiate in 2024 New Programs 5+ additional unnamed research programs
Relay Tx – Milestones 2024-25 Breast Cancer Portfolio Milestones RLY-1013 ERα PI3Kα RLY-2608 RLY-2139 CDK2 IND-ready in 2025 Data update in 4Q 2024 Doublet safety & efficacy data Initial triplet data CDK4i triplet clinic start by YE 2024 Potential pivotal trial start in 2025 IND-ready Genetic Disease Portfolio milestones New Program Fabry Clinical start in 2H 2025 New Program VM Clinical start in 1Q 2025 Solid Tumors portfolio milestones New Program NRAS Clinical start in 2H 2025 Lirafugratinib FGFR2 Tumor agnostic data & regulatory update in 2H 2024 Migoprotafib SHP2 Three ongoing combo trials* * Genentech controls data disclosures ~$750M cash as of end Q1 2024 Expected to fund current operating plan into 2H 2026 Dynamo™ Platform 5+ unnamed research programs
PI3Kα – Large Opportunity Across Indications and Therapeutic Areas PIK3CA mutant HR+/HER2- Breast Cancer PIK3CA mutant Vascular Malformations PIK3CA mutant Other Solid Tumors Cerebral Cavernous Lymphatic Venous PROS 65k pt 65k pt 25k pt 15k pt ~150k Patients (US prevalence)1 ~170k Patients (US prevalence)2 Colorectal Endometrial Bladder Prostate NSCLC HNSCC 28k pt 20k pt 17k pt 16k pt 14k pt 9k pt Relay Tx's PI3Kα Franchise has the potential to address wide range of large disease indications Adjuvant 1st Line 2nd Line 120k pt 18k pt 14k pt ~160k Patients (US incidence)3 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (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 (SEER; 3rd party source for alteration rate, May 2024) RLY-2608 RLY-2608 Potential for rapid POC with RLY-2608, then distinct molecule for pivotal
Relay Tx – Extensive Breast Cancer Portfolio in Validated Market Expected to Grow to ~$27B by 20301 …for which Relay Tx’s broad next generation ER+/HER2- BC Portfolio is designed to address HR+/HER2- Breast Cancer is a very large patient population… ~150k US prevalence HR+/HER2- Breast Cancer Patients with PI3Kα mutation2 Evolving SoC PI3Kα Mutant-specific ER Degraders & other SERDs CDK4 or CDK2 selective Current SoC Tx PI3Kα Pathway Non-Selective Inhibitors ET Backbone: AI / fulvestrant CDK4/6 inhibitors RLY-2608 (pan) RLY-1013 (ERα) RLY-2139 (CDK2)3 Atirmo (CDK4) 35% of Breast Cancer Pt with PI3Kα mutation (14% of all solid tumors) ~120k Adjuvant ~18k 1L ~14k 2L 1. Decision Resources Group – Breast Cancer Disease Landscape & Forecast (Nov 2023); 2. Prevalent US patient population with a PIK3CA mutation in each line of therapy (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 3. RLY-2139 is paused and IND-ready
RLY-2608 + Atirmociclib (CDK4i): Pfizer – Relay Tx Clinical Trial Collaboration Potentially Differentiated Safety and Tolerability Profile Encouraging Efficacy Data in Heavily Pre-Treated Patients Source: Pfizer Oncology Innovation Day presentation, Feb 2024
RLY-2608 – Broad Development Program: Doublet Mono Dose Escalation RLY-2608 + Fulvestrant Doublet RLY-2608 + Fulvestrant + CDKi Triplet Dose Expansion Ongoing ReDiscover Trial Initiated 2024 Completed (Started Apr 2022) 400mg BID (n=20) 600mg BID (n=60) Enrolling 600mg BID (N=17) 400mg BID (N=10) 20 pt enrolled before YE 2023 Enrolling Enrolling Enrolling Data Expectations for YE2024 Disclosure All Doses 600mg BID >60 pts >100 pts >40 pts Safety Evaluable 6+ mo Follow-up Triplet: Early safety and tolerability data Doublet Landmark PFS analysis
RLY-2608 – Broad Development Program: Triplet Mono Dose Escalation RLY-2608 + Fulvestrant Doublet RLY-2608 + Fulvestrant + CDKi Triplet Dose Expansion Ongoing ReDiscover Trial Completed (Started Apr 2022) 400mg BID (n=20) 600mg BID (n=60) Enrolling 600mg BID (N=17) 400mg BID (N=10) 20 pt enrolled before YE 2023 Enrolling Enrolling Data Expectations for YE2024 Disclosure All Doses 600mg BID >60 pts >100 pts >40 pts Safety Evaluable 6+ mo Follow-up Doublet Landmark PFS analysis Triplet: Early safety and tolerability data Ribo (CDK4/6) Atirmo (CDK4) Enrolling Clinical start in 2024 Initiated 2024
RLY-2608 – Broad Development Program: Mono Dose Escalation RLY-2608 + Fulvestrant Doublet RLY-2608 + Fulvestrant + CDKi Triplet Dose Expansion ReDiscover Trial Completed (Started Apr 2022) Enrolling 600mg BID (N=17) 400mg BID (N=10) Enrolling Data Expectations for YE2024 Disclosure All Doses 600mg BID >60 pts >100 pts >40 pts Safety Evaluable 6+ mo Follow-up Doublet Landmark PFS analysis Triplet: Early safety and tolerability data Ribo (CDK4/6) Atirmo (CDK4) Enrolling Clinical start in 2024 Initiated 2024 Mono Ongoing Enrolling PRs seen in multiple tumor types* * PRs include both confirmed and unconfirmed partial responses 400mg BID (n=20) 600mg BID (n=60) 20 pt enrolled before YE 2023
RLY-2608 – Broad Development Program Dose Escalation RLY-2608 + Fulvestrant Doublet RLY-2608 + Fulvestrant + CDKi Triplet Dose Expansion ReDiscover Trial Completed (Started Apr 2022) 400mg BID (n=20) 600mg BID (n=60) Enrolling 600mg BID (N=17) 400mg BID (N=10) 20 pt enrolled before YE 2023 Enrolling Data Expectations for YE2024 Disclosure All Doses 600mg BID >60 pts >100 pts >40 pts Safety Evaluable 6+ mo Follow-up Doublet Landmark PFS analysis Triplet: Early safety and tolerability data Ribo (CDK4/6) Atirmo (CDK4) Enrolling Clinical start in 2024 Initiated 2024 Mono Ongoing Enrolling PRs seen in multiple tumor types* ReDiscover trial continues broad enrollment across ~25 sites in ~5 countries * PRs include both confirmed and unconfirmed partial responses
Breast Cancer – Large Market in Current and Emerging Standards of Care Endocrine Sensitive CDK4 + next gen oral ET Oral SERD monoTx Inavolisib + palbo + fulv Inavolisib + fulvestrant ADCs 11,000 pts Endocrine Resistant Capivasertib + fulvestrant or Alpelisib + fulvestrant or Everolimus + AI Elacestrant (ESR1m) Chemotherapy CDK4/6 + fulvestrant Chemotherapy CDK4/6 + AI (abema / ribo / palbo) PIK3CA mutated HR+/HER2- BC Treatment Paradigm1 7,000 pts 14,000 pts Fulvestrant (ESR1WT) Current Standard of Care Emerging TX RLY-2608 combinations Current PI3Kα Pathway Total Addressable Market2 (Metastatic HR+/HER2- Breast Cancer) $6B+ 1L 2L 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (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)
RLY-2608 – 2L PFS Pivotal Benchmark: ~6 Months 1. SABCS 2021 #P5-17-05; 2. Rugo 2021 Lancet Oncol 22:489, ASCO 2023 1078; 3. Turner N Engl J Med 2023; 388:2058-2070; 4. Based on 4.0-6.2mo mPFS reported in Novartis-sponsored real-world evidence study for alpelisib + fulvestrant (ASCO 2022 #1055); 5. 5.5mo mPFS reported in CDK4/6-experienced patient sub-population of CAPItello-291 Note: These data are derived from different clinical trials at different points in time, with differences in trial design and patient populations. As a result, cross-trial comparisons cannot be made, and no head-to-head clinical trials have been conducted. % prior fulv N Doublet Combination Regimens Capivasertib + fulvestrant CAPItello-2913 0% 355 Alpelisib + fulvestrant BYLieve2 0% 127 Ph1b Arm D1 Inavolisib + fulvestrant 47% 60 29% 56% 19% 46% 19% 48% Data Benchmark FDA Approval Approved 2023 Approved 2019 6.2mo 5.5mo 7.1mo 8.0mo 7.3mo Not approved ORR CBR 5.5mo5 6.2mo4 mPFS Capi ORR & CBR include 30% of pts who are CDK4/6-naïve
Relay Tx – Milestones 2024-25 Breast Cancer Portfolio Milestones RLY-1013 ERα RLY-2139 CDK2 IND-ready in 2025 IND-ready Genetic Disease Portfolio milestones Solid Tumors portfolio milestones New Program NRAS Lirafugratinib FGFR2 Tumor agnostic data & regulatory update in 2H 2024 Migoprotafib SHP2 Three ongoing combo trials* * Genentech controls data disclosures New Program Fabry Clinical start in 2H 2025 New Program VM Clinical start in 1Q 2025 Clinical start in 2H 2025 Dynamo™ Platform 5+ unnamed research programs PI3Kα RLY-2608 Data update in 4Q 2024 Doublet safety & efficacy data Initial triplet data CDK4i triplet clinic start by YE 2024 Potential pivotal trial start in 2025
CDK4i clinical start by YE 2024 ~28,000 pts4 ~170,000 pts2 (chronic treatment) Clinical start in 2H 2025 1st PI3Kαi + ET + CDK4i combination in clinic 1st NRAS-selective inhibitor Clinical start in 1Q 2025 1st mutant-selective PI3Kα inhibitor Clinical start in 2H 2025 1st non-inhibitory αGal chaperone Solid Tumors Relay Tx – Today’s Updates NRAS-Driven Solid tumors PI3Kα-Driven Breast Cancer 1 4 PI3Kα-Driven Vascular Malformations 2 Fabry Disease 3 BREAST CANCER ~150,000 pts1 ~8,000 pts3 (chronic treatment) Milestones Large US opportunity Program Updates GENETIC DISEASE 1. Prevalent US patient population with a PIK3CA mutation in adjuvant, first line metastatic and second line metastatic settings (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalence of vascular malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources); 3. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 4. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024)
~170,000 patients1 (chronic treatment) Limited efficacy Lack of selectivity Approved Tx for PROS only Vijoice® (alpelisib) approved PIK3CAmut 1st mutant-selective PI3Kα inhibitor PI3Kα-Driven Vascular Malformations – Significant Unmet Need First Mutant Selective Inhibitor Dynamo™ Platform GENETIC DISEASE PI3Kα-Driven Vascular Malformations Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach 1. Prevalence of Vascular Malformations with a PIK3CA mutation (sources: Keppler-Noreuil. Am J Med Genet A. 2015; Engel-Nitz. JVA. 2022; Rodriguez-Laguna; OJRD. 2022; Vogel. Ped Derm. 2013; Shah. J Maxillofac Oral Surg. 2010; Poget. Ped Surg Int. 2023; Behravesh; CDT. 2016; Peyre. NEJM. 2021; Fereydooni et al 2019; Penington et al 2023; Gallagher et al 2022; Luks et al 2015; Limaye et al 2015; Stor et al 2023; Broek et al 2019; Choquet et al 2015; Venot et al. 2018; Pagliazzi et al 2021)
Dr. Adrienne Hammill, MD PhD 25 PhD in Cell Regulation “Asymmetric cell division results in differential apoptotic cell fates in a B-cell lymphoma model of tumor dormancy” Board certified in Pediatrics and Pediatric Hematology-Oncology Certificate in Clinical and Translational Research Working in vascular anomalies since 2009 Serving as Research Director of the Hemangioma & Vascular Malformations Center (HVMC) Director, Cincinnati HHT Center of Excellence Director, Cincinnati Sturge-Weber Center of Excellence/Clinical Care Network Center
Vascular Anomalies Dr. Adrienne Hammill, MD PhD 26 Anomalies is an umbrella term for many different diagnoses Includes TUMORS “things that grow” and MALFORMATIONS “present since birth” Distinction less clear than it used to be, a few “unclassified” Vascular Anomalies overall not rare due to high frequency of hemangiomas But many of the individual diagnoses are quite rare
Vascular Malformations Dr. Adrienne Hammill, MD PhD 27 Vascular malformations can include a single type of malformed vessel, or combinations of vessels
Vascular Malformations Dr. Adrienne Hammill, MD PhD 28 Vascular malformations can be localized (“isolated”), diffuse/multifocal, or part of a syndrome with other findings Most frequent syndromic association is overgrowth, particularly in “combined vascular malformations” A range of severity in Vascular Anomalies Sources: Colmenero 2021; Davidson et al, 2015; de Grazia et al Isolated Diffuse, Syndromic
Genetic Causes of Vascular Malformations – Germline Mutations Dr. Adrienne Hammill, MD PhD Key: Cell Membrane Receptor Tyrosine Kinases G-Protein Coupled Receptors PI3K AKT/PKB mTOR S6 eIF-4E Protein Synthesis VEGF Gα TIE2 RAS PTEN TSC1 TSC2 RASA1 PTEN-associated VAs/hamartomas TS-associated angiofibromas CM-AVM, Parkes-Weber RAF MEK ERK EGFR/ VEGFR = known oncogene = known tumor suppressor = vascular anomalies = non-oncogene driver 29
Genetic Causes of Vascular Malformations – Somatic Mutations Dr. Adrienne Hammill, MD PhD Key: Cell Membrane Receptor Tyrosine Kinases G-Protein Coupled Receptors PI3K AKT/PKB mTOR S6 eIF-4E Protein Synthesis VEGF Gα TIE2 RAS PTEN TSC1 TSC2 RASA1 VMCM, BRBNS, sporadic VMs Sturge-Weber syndrome, CM (port wine birthmark) RAF MEK ERK KLA, GSD RICH, NICH EGFR/ VEGFR = known oncogene = known tumor suppressor = vascular anomalies = non-oncogene driver 30 Proteus LM, VM, PROS, GLA
Genetic Causes of Vascular Malformations Dr. Adrienne Hammill, MD PhD Key: Cell Membrane Receptor Tyrosine Kinases G-Protein Coupled Receptors PI3K AKT/PKB mTOR S6 eIF-4E Protein Synthesis VEGF Gα TIE2 RAS PTEN TSC1 TSC2 RASA1 VMCM, BRBNS, sporadic VMs PTEN-associated VAs/hamartomas TS-associated angiofibromas Proteus Lymphedema CM-AVM, Parkes-Weber Sturge-Weber syndrome, CM (port wine birthmark) RAF MEK ERK KLA, GSD RICH, NICH EGFR/ VEGFR = known oncogene = known tumor suppressor = vascular anomalies = non-oncogene driver 31 LM, VM, PROS, GLA
PIK3CA-related Overgrowth Spectrum (PROS) Phenotypes Sources: Mirzaa G et al. PIK3CA-Related Overgrowth Spectrum. 2013 Aug 15 [Updated 2023 Apr 6]. In: GeneReviews® [Internet] Megalencephaly-capillary malformation (MCAP) syndrome Dysplastic megalencephaly (DMEG), hemimegalencephaly (HMEG) and focal cortical dysplasia (FCD) Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal (CLOVES) syndrome Klippel-Trenaunay syndrome (KTS) Capillary malformation of the lower lip, Lymphatic malformation of the face and neck, Asymmetry of face and limbs, Partial/generalized Overgrowth (CLAPO) syndrome Fibroadipose hyperplasia or overgrowth (FAO) Hemihyperplasia multiple lipomatosis (HHML) Facial infiltrating lipomatosis (FIL) Macrodactyly Isolated tissue dysplasia/overgrowth phenotypes: lymphatic malformations, venous malformations, lipomatosis Dr. Adrienne Hammill, MD PhD 32
PI3Kα-Driven Vascular Malformations – Overview of Biology ~300k US patients affected by Vascular Malformations, driven by prenatal somatic mutations Abnormal development of lymphatic and/or blood vessels leads to a wide range of symptoms Malformations may involve one or more types of vasculature Mutation Frequency by Gene PIK3CA TIE2 Other CCM1-3 Approx. 170k pts in the US Dr. Adrienne Hammill, MD PhD 33 Sources: Fereydooni et al 2019, Penington et al 2023, Gallagher et al 2022, Luks et al 2015, Limaye et al 2015, Stor et al 2023, Broek et al 2019, Choquet et al 2015, Venot et al. 2018, Pagliazzi et al 2021; Photo sources: Delestre et al 2021, Pagliazzi et al, 2021 Note: TIE2 gene also refers to TEK gene
PI3Kα-Driven Vascular Malformations – Patient Treatment Journey Symptom Presentation Diagnosis Treatment PCP, Dermatologist, Surgeon, ENT, etc. Geneticist, “Vascular Anomalist” Surgeon, Int. Radiologist, Dermatologist, Heme-Onc Watch and wait; Compression Therapy Local Treatment: Laser, sclerotherapy, surgery Systemic Therapy: alpelisib, sirolimus Invasive, recurrence is common (~25-40% recurrence rate) Incomplete responses, side effects / toxicities limit widespread use Frequency of use Temporary; 50-75% of diagnosed pts receive local or systemic Tx Current unmet need for selective, systemic therapy for Vascular Malformations Referral Pathway Treatment & Ongoing Management Dr. Adrienne Hammill, MD PhD 34 Source: primary research
PI3Kα-Driven 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 Vascular Malformation Types Dr. Adrienne Hammill, MD PhD 35 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
Non-Selective Limited scope, approved in PROS only Not approved in any Vascular Malformation types Non-Selective Immunosuppressive Alpelisib Lymphatic Malformations (LM) Venous Malformations (VM) Cerebral Cavernous Malformations (CCM) PIK3CA-Related Overgrowth Spectrum (PROS) PI3Kα-Driven Vascular Malformations – Systemic Tx Limited by Non-Selective SoC Limited Efficacy - 27% ORR1 1. ORR defined as radiologic response ≥20% lesion reduction; Source: FDA label for VIJOICE® Sirolimus
Favorable Selectivity Favorable Tolerability Favorable Efficacy PI3Kα-Driven Vascular Malformations – Relay Tx Mutant Selective Approach Selective for mutant PI3Kα Fewer key common PI3K class AEs* Reduction of mutant PIK3CA ctDNA* 6% 10% 59% 60% 29% RLY-26081 Alpelisib2 *interim data from oncology trials1-2 1. Interim AE rates and ctDNA for RLY-2608 part of ongoing ReDiscover trial studying solid tumors (oncology), data as of 07/24/23; 2. Alpelisib AE rates from BYLieve study (oncology), Rugo 2021 Lancet Oncol 22:489 RLY-26081 Potential for rapid POC with RLY-2608, then use a distinct molecule for pivotal studies Lymphatic Malformations (LM) Venous Malformations (VM) Cerebral Cavernous Malformations (CCM) PIK3CA-Related Overgrowth Spectrum (PROS) Hyper- glycemia Diarrhea 6% 6% Rash 12% Grade 1-2 Grade 3+
PI3Kα – Dynamo™: Integration of Experimental and Computational Tools Discovery of 1st mutant-selective PI3Kα inhibitor Target Modulation Hypothesis Hit Identification Lead Optimization CryoEM & X-ray Crystallography Long Time-scale MD DNA-Encoded Libraries (DEL) Differential Dynamics Integrated Pharmacology PK / PD Dose Modeling Platform Tool Examples Solved 1st full-length structures & novel pocket of PI3Kα Identified early chemical matter for mutant selectivity Rapidly designed the 1st mutant-selective inhibitor of PI3Kα 1 2 3 Computational tool Experimental tool
~170,000 patients1 (chronic treatment) Limited efficacy Lack of selectivity Approved Tx for PROS only Vijoice® (alpelisib) approved PIK3CAmut 1st mutant-selective PI3Kα inhibitor Clinical Start in Q1 2025 PI3Kα-Driven Vascular Malformations – Significant Unmet Need GENETIC DISEASE PI3Kα-Driven Vascular Malformations Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach 1. Prevalence of Vascular Malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources) Genetic Disease Portfolio milestones
CDK4i clinical start by YE 2024 ~28,000 pts4 ~150,000 pts1 ~170,000 pts2 (chronic treatment) ~8,000 pts3 (chronic treatment) Clinical start in 2H 2025 1st PI3Kαi + ET + CDK4i combination in clinic 1st NRAS-selective inhibitor Clinical start in 1Q 2025 1st mutant-selective PI3Kα inhibitor Clinical start in 2H 2025 1st non-inhibitory αGal chaperone Solid Tumors Relay Tx – Today’s Updates NRAS-Driven Solid tumors PI3Kα-Driven Breast Cancer 1 4 PI3Kα-Driven Vascular Malformations 2 Fabry Disease 3 BREAST CANCER GENETIC DISEASE 1. Prevalent US patient population with a PIK3CA mutation in adjuvant, first line metastatic and second line metastatic settings (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalence of vascular malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources); 3. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 4. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024) Milestones Large US opportunity Program Updates
~8,000 patients1 (chronic treatment) Limited αGal activation & limited mutational coverage Galafold® (migalastat) approved in Fabry Disease GLA mutations 1st non-inhibitory αGal chaperone Fabry Disease – Large Validated Market With Significant Unmet Need First Non-Inhibitory αGal Chaperone Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach Dynamo™ Platform GENETIC DISEASE Fabry Disease 1. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024)
~$1.6B peak sales1 Fabry Disease – Large Validated Market With Significant Unmet Need Over 1,000 different GLA gene mutations Reduces αGal protein levels Leads to accumulation of toxic Gb3 substrate Broad clinical manifestations; Life threatening cardiac & renal disfunction Fabry disease is a lysosomal storage disorder affecting ~8,000 patients in US Current therapies have established a market but have key limitations Current Therapies Limited αGal activation Limited mutational coverage Not combined with ERT Limitations of Inhibitory Chaperone 1 2 3 Inhibitory Chaperone Therapy (migalastat) Need for a non-inhibitory αGal chaperone ~$780M peak sales2 40% of pts Enzyme Replacement Therapy (ERT, intravenous) 1. Combination of Fabrazyme® (~$1,100M) and Replagal® (~$480M) 2030 forecasted WW sales per EvaluatePharma, April 2024; 2. Galafold® 2030 forecasted WW sales per EvaluatePharma, April 2024
αGal Inhibitory vs Non-Inhibitory Chaperone Normal Mutant Fabry Disease – Dynamo™ Discovered a Novel Allosteric Pocket Active Site
Fabry Disease – Dynamo™: Integration of Experimental and Computational Tools Discovery of 1st non-inhibitory αGal chaperone Discovered & validated novel allosteric pocket Identified & validated initial hits that stabilized Achieved potent αGal non-inhibitory chaperones 1 2 3 Computational tool Experimental tool Target Modulation Hypothesis Hit Identification Lead Optimization Structure Ensembles Long Time-Scale MD NMR Virtual Screening HTP Automated Chem. ADME/PK Models Platform Tool Examples
Fabry Disease – Relay Tx Compounds are Non-Inhibitory Chaperones Migalastat inhibited αGal function while Relay Tx compounds did not Note: Biochemical assay run with WT αGal; 1 hr incubation at room temperature
Fabry Disease – Potential Benefits of Non-Inhibitory Chaperone Approach Superior αGal activation1 Broad mutational coverage2 Combinable with ERT3 1 2 3 Relay Tx Solution: Non-Inhibitory Chaperone to Stabilize Protein and Increase Activity Notes: 1. R301Q mut αGal (2hr post compound washout, expressed in GLA KO HEK293 cells); In vitro αGal activity assay (4MU) across multiple GLA mutations expressed in HEK293 GLA KO cells (assessed at 1uM); 3. GLA KO mouse model, activity assessed following single dose of ERT and 14-day treatment with RTX-1
There were no adverse findings in an exploratory rat toxicology study of RTX-1 at exposures equivalent to 100 mg/kg BID Superior αGal Activation 1 Relay Tx Non-Inhibitory Chaperones Can Lead to Higher Levels of In Vivo Activity
Relay Tx Non-Inhibitory Chaperones Have Broad Mutational Coverage In vitro αGal activity assay (4MU) across multiple GLA mutations expressed in HEK293 GLA KO cells Amenable | Non-Amenable (as per migalastat label) Broad Mutational Coverage 2 Note: αGal activity evaluated at 1uM of migalastat and RTX-1
Relay Tx Non-Inhibitory Chaperones Combinable with ERT Combinable with ERT 3
~8,000 patients1 (chronic treatment) Limited αGal activation & limited mutational coverage Galafold® (migalastat) approved in Fabry Disease GLA mutations 1st non-inhibitory αGal chaperone Fabry Disease – Large Validated Market With Significant Unmet Need Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach GENETIC DISEASE Fabry Disease 1. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024) Clinical Start in 2H 2025 Genetic Disease Portfolio milestones
CDK4i clinical start by YE 2024 ~150,000 pts1 ~28,000 pts4 ~170,000 pts2 (chronic treatment) ~8,000 pts3 (chronic treatment) Clinical start in 2H 2025 1st PI3Kαi + ET + CDK4i combination in clinic 1st NRAS-selective inhibitor Clinical start in 1Q 2025 1st mutant-selective PI3Kα inhibitor Clinical start in 2H 2025 1st non-inhibitory αGal chaperone Relay Tx – Today’s Updates NRAS-Driven Solid tumors PI3Kα-Driven Breast Cancer 1 4 PI3Kα-Driven Vascular Malformations 2 Fabry Disease 3 BREAST CANCER GENETIC DISEASE Solid Tumors 1. Prevalent US patient population with a PIK3CA mutation in adjuvant, first line metastatic and second line metastatic settings (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalence of Vascular Malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources); 3. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 4. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024) Milestones Large US opportunity Program Updates
~28,000 patients1 Lack of selectivity Challenging AE profile Limited efficacy Non-selective RAF/MEK/Pan-RAS NRASmut 1st NRAS-selective inhibitor NRAS – Large Validated Market With Significant Unmet Need First NRAS Selective Inhibitor Dynamo™ Platform Solid Tumors NRAS-Driven Solid Tumors Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach 1. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding stage 0-II newly diagnosed melanoma patients (SEER, 3rd party source for alteration rate, Jan 2024)
NRAS – Large Validated Market With Significant Unmet Need NRAS mutations observed in broad range of tumor types NRAS mutations are a key driver of solid tumors, though no NRAS-selective agent exists Head and Neck NSCLC Melanoma2 X ~0.6k ~2.2k ~4.0k ~0.4k ~6.4k ~1.1k Pancreatic Cancer Colorectal (CRC) Bladder Cancer Thyroid Cancer ~5.9k Annual US Patients1 RAF MEK ERK Cell growth and proliferation NRAS HRAS KRAS Downstream RAS pathway (pan-RAF, MEK, ERK) Pan-RAS mut c 1. Newly diagnosed (incident) patients with an NRAS mutation for each tumor type (SEER, 3rd party source for alteration rate, Jan 2024); 2. Melanoma includes incident stage III and IV patients only (excludes stage 0-II patients)
based MEK + RAFi Pan-RAS Limited Therapeutic Window of Current Agents – Pan-RAF/RAS & MEK Inhibitors Limited Efficacy Limited Tolerability MEK + RAFi Pan-RAS Rash Liver Tox 25-80% <10-60% 81% 7-8% Limited Target Inhibition Dose Red. Dose Discont. 16-70% 7-28% 8% 1% High rates of skin toxicity driven by off-target pan-RAS pathway inhibition RAF MEK ERK Cell growth and proliferation NRAS HRAS KRAS Downstream RAS pathway (pan-RAF, MEK, ERK) Pan-RAS mut Regimen (2L NRASmut melanoma) ORR PFS (mo) Naporafenib (RAFi) + trametinib (MEKi) 13-47% 4.2-5.5 Belvarafenib (RAFi) + cobimetinib (MEKi) 39% 7.3 Non-Selective Agents in Development No guidance for Ph3 development Sources: ASCO 2021 #3007 (Belvarafenib + cobimetinib, n=32 all, 13 for efficacy), de Braud 2023 J Clin Oncol 41:2651 (naporafenib + trametinib, n=30 expansion arm), ASCO 2023 #9510 (tunlametinib, n=95), ESMO 2023 652O (RMC-6236, n=111 pts at ≥80mg; liver tox = elevated ALT/AST
NRAS – Dynamo™ Platform Discovered a Novel Allosteric Pocket Exploited differences in protein motion… …to design first NRAS-selective inhibitor NRAS HRAS KRAS NRAS HRAS KRAS
NRAS – Dynamo™: Integration of Experimental and Computational Tools Discovery of 1st NRAS-selective inhibitor Discovered a novel cryptic pocket Identified & validated hits selective for NRAS (over H/KRAS) Rapidly designed & prioritized NRAS inhibitors 1 2 3 Target Modulation Hypothesis Hit Identification Lead Optimization X-ray Fragment Screen Virtual Screening 2D NMR Computational Fragment Merging High Throughput Automated Chem. Free Energy Calculations Platform Tool Examples Computational tool Experimental tool
NRAS Inhibitors Are Potent, Selective & Active Across NRAS Mutations 1. Based on SPR analysis of purified protein; 2. Based on pERK assay of SK-MEL-2, SK-MEL-30, and CALU-6 cell lines evaluated at 24hr timepoint; 3. Based on cell proliferation panel (17 cell lines) evaluated at 3-5d timepoint depending on cell line
*Regressions also achieved with additional NRAS mutant models (NRAS Q61K and NRAS Q61R) NRAS Inhibitors Achieve Complete Regression at Well Tolerated Doses There were no adverse findings in an exploratory rat toxicology study of RTX-2 at exposures equivalent to 100mg/kg QD
~28,000 patients1 Lack of selectivity Challenging AE profile Limited efficacy Non-selective RAF/MEK/Pan-RAS NRASmut 1st NRAS-selective inhibitor NRAS – Large Validated Market With Significant Unmet Need Solid Tumors NRAS-Driven Solid Tumors Genetically Defined Clinically Validated Unmet Medical Need Commercially Attractive Novel Approach 1. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding stage 0-II newly diagnosed melanoma patients (SEER, 3rd party source for alteration rate, Jan 2024) Clinical Start in 2H 2025 Solid Tumors Portfolio Milestones
Solid Tumors BREAST CANCER Relay Tx – Today’s Updates NRAS-Driven Solid tumors PI3Kα-Driven Breast Cancer 1 4 CDK4i clinical start by YE 2024 Clinical start in 2H 2025 ~150,000 pts1 ~28,000 pts4 1st PI3Kαi + ET + CDK4i combination in clinic 1st NRAS-selective inhibitor PI3Kα-Driven Vascular Malformations 2 Clinical start in 1Q 2025 ~170,000 pts2 (chronic treatment) 1st mutant-selective PI3Kα inhibitor Fabry Disease 3 Clinical start in 2H 2025 ~8,000 pts3 (chronic treatment) 1st non-inhibitory αGal chaperone GENETIC DISEASE 1. Prevalent US patient population with a PIK3CA mutation in adjuvant, first line metastatic and second line metastatic settings (Global Data HR+/HER2- Breast Cancer Global Forecast, November 2023; 3rd party source for alteration rate); 2. Prevalence of vascular malformations with a PIK3CA mutation (Gallagher et al 2022 and several other sources); 3. Prevalence of Fabry patients (National Fabry Disease Foundation, Jan 2024); 4. Newly diagnosed (incident) solid tumors with an NRAS mutation, excluding melanoma stages 0-II (SEER, 3rd party source for alteration rate, Jan 2024); 5. Fabry disease forecasted 2024 market size per EvaluatePharma, includes Galafold® and ERTs (May 2024) Milestones Large US opportunity Program Updates Ongoing mono, doublet, triplet; Data update YE24 $2B current market5
PI3Kα – Large Opportunity Across Indications and Therapeutic Areas PIK3CA mutant HR+/HER2- Breast Cancer PIK3CA mutant Vascular Malformations PIK3CA mutant Other Solid Tumors Cerebral Cavernous Lymphatic Venous PROS 65k pt 65k pt 25k pt 15k pt ~150k Patients (US prevalence)1 ~170k Patients (US prevalence)2 Colorectal Endometrial Bladder Prostate NSCLC HNSCC 28k pt 20k pt 17k pt 16k pt 14k pt 9k pt Relay Tx's PI3Kα Franchise has the potential to address wide range of large disease indications Adjuvant 1st Line 2nd Line 120k pt 18k pt 14k pt ~160k Patients (US incidence)3 1. Prevalent US patient population with a PIK3CA mutation in each line of therapy (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 (SEER; 3rd party source for alteration rate, May 2024) RLY-2608 RLY-2608 Potential for rapid POC with RLY-2608, then distinct molecule for pivotal
Relay Tx Dynamo™ – Internalizing Bespoke Tools In-House Molecular Dynamics (MD) In-House REL-DEL In-House High-Throughput Automated Chemistry Dynamo™ Platform Development & Commercial Target Identification Target Modulation Hypothesis Hit Identification Lead Optimization
Free energy calculations Digitally encoded libraries Long time-scale MD Differential dynamics Automated Chemical Design Generative design Active learning ADME/PK models ML-DEL + AI models for DEL Giga-scale virtual screening Computational fragment merging COMPUTATION EXPERIMENTATION Relay Tx Dynamo™ – Continuing to Focus, Build and Evolve Dynamo™ Platform integrates industry-leading tools and will continue to quickly grow and evolve PEOPLE NMR X-ray fragment screening HDX-MS Mechanistic enzymology Cryo-EM REL-DEL Integrated pharmacology Protein design and engineering Ambient temp. X-Ray crystallography Automated Ligand ID System (ALIS) Structure ensembles High throughput automated chemistry
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 Monotherapy FGFR2 Lirafugratinib (RLY-4008) SHP2 Migoprotafib (GDC-1971) Paused; IND ready Advance to IND-ready 3 ongoing combo studies (GNE) CDK4i triplet to initiate in 2024 New Programs 5+ additional unnamed research programs
Relay Tx – Milestones 2024-25 Breast Cancer Portfolio Milestones RLY-1013 ERα PI3Kα RLY-2608 RLY-2139 CDK2 IND-ready in 2025 Data update in 4Q 2024 Doublet safety & efficacy data Initial triplet data CDK4i triplet clinic start by YE 2024 Potential pivotal trial start in 2025 IND-ready Genetic Disease Portfolio milestones New Program Fabry Clinical start in 2H 2025 New Program VM Clinical start in 1Q 2025 Solid Tumors portfolio milestones New Program NRAS Clinical start in 2H 2025 Lirafugratinib FGFR2 Tumor agnostic data & regulatory update in 2H 2024 Migoprotafib SHP2 Three ongoing combo trials* * Genentech controls data disclosures ~$750M cash as of end Q1 2024 Expected to fund current operating plan into 2H 2026 Dynamo™ Platform 5+ unnamed research programs
