UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 11, 2021

 

 

FORMA THERAPEUTICS HOLDINGS, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-39333   37-1657129

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

Forma Therapeutics Holdings, Inc.

500 Arsenal Street, Suite 100

Watertown, Massachusetts 02472

(Address of principal executive offices, including zip code)

(617) 679-1970

(Registrant’s telephone number, including area code)

Not Applicable

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

 

 

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

 

☐

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

 

☐

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

 

☐

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

 

☐

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

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

 

Title of each class

 

Trade

Symbol(s)

 

Name of each exchange

on which registered

Common Stock, $0.001 par value per share   FMTX   The Nasdaq Global Market

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

Emerging growth company  ☒

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

 

 

 

Item 7.01.

Regulation FD Disclosure.

On June 11, 2021, Forma Therapeutics Holdings, Inc. (the “Company”) issued a press release titled “Forma Therapeutics Presents New Phase 1 Data on Etavopivat (formerly referred to as FT-4202) at 26th European Hematology Association Congress,” a copy of which is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K.

In addition, the Company has made available on its website the Company’s presentation from the 2021 European Hematology Association’s (“EHA”) Virtual Congress. The presentation has been added to the Company’s website at https://ir.formatherapeutics.com/. A copy of the presentation is furnished herewith as Exhibit 99.2 to this Current Report on Form 8-K.

The information in this Item 7.01, including Exhibits 99.1 and 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, 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, except as expressly set forth by specific reference in such filing.

 

Item 8.01.

Other Events.

On June 11, 2021, the Company announced new data from its ongoing Phase 1 trial of etavopivat (formerly referred to as FT-4202). The announcement included initial data from the open-label extension (“OLE”) cohort studying etavopivat’s effects on hematologic and hemolytic parameters for patients living with sickle cell disease (“SCD”) receiving 400 mg etavopivat once-daily for at least two weeks and up to 12 weeks. Also announced were the unblinded results from two multiple ascending dose (“MAD”) cohorts, which demonstrated the effects once-daily dosing of 300 mg or 600 mg etavopivat for 14 days on measures of sickle red blood cell (“RBC”) functional health.

Clinical Data Results

In the combined (300 mg QD) and MAD2 (600 mg QD) cohorts, 73% (11 of 15) of patients achieved a hemoglobin increase of greater than 1g/dL over baseline; significant improvement in hematologic and hemolytic markers also include decreased absolute reticulocytes (100%, or 15 of 15), decreased LDH levels (73%, or 11 of 15) and decreased indirect bilirubin levels (93%, or 14 of 15). The osmoscan and oxygenscan results from 14 patients showed a statistically significant improvement.

Initial results as of May 24, 2021, in the OLE cohort for eight patients receiving once-daily etavopivat treatment (400 mg) for at least 2 weeks indicated a hemoglobin increase of greater than 1 g/dL in 88% (7 of 8), with a mean hemoglobin increase of 1.5 g/dL. Patient data indicated a durable response for those patients receiving treatment beyond two weeks for up to 12 weeks, with improved hematologic and hemolytic parameters. The improvement in RBC functional health extended beyond the 12-week treatment period; in one patient, improved sickle RBC deformability remained for up to four weeks after treatment discontinuation. These initial OLE data support the combined MAD cohort results and show that daily etavopivat treatment also significantly improved hematologic and hemolytic parameters.

The safety profile in the OLE cohort was consistent with underlying disease. Of note, two patients reported serious adverse events, including one vaso-occlusive crisis and acute chest syndrome, which was not considered related to treatment by the trial investigator. A deep-vein thrombosis (DVT) report was described as possibly related.

The disclosure under this Item 8.01 contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the Company’s beliefs and expectations regarding: initial results to date for the etavopivat open label extension cohort of the Company’s Phase 1 clinical trial; the therapeutic potential, clinical benefits and safety related to etavopivat; whether initial results from the Company’s clinical trials are predictive of final trial results or future clinical studies; and the Company’s planned presentation of data at 2021 EHA Virtual Congress. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar 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

 

2

limitation, those risks and uncertainties related the Company’s ability to execute on its strategy; the therapeutic potential and safety of etavopivat; the timing and completion of the Company’s Phase 1 study of etavopivat and final audit and quality controlled verification of initial data and related analyses; the timing and success of the Company’s Phase 2/3 Hibiscus Study of etavopivat in SCD patients; positive results from initial data analyses may not be predictive of final results; risks related to the Company’s planned regulatory submissions and developments; and other risks identified in the Company’s SEC filings, including those risks discussed under the heading “Risk Factors” in the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, as well as other risks detailed in the Company’s subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. The Company disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statement included in this Item 8.01 speaks only as of the date on which it was made. The Company undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

 

Item 9.01.

Exhibits

(d) Exhibits

 

99.1   

Press release issued by Forma Therapeutics Holdings, Inc. on June  11, 2021, furnished herewith.

99.2    Forma Therapeutics Holdings, Inc. Corporate Presentation, dated June 11, 2021, furnished herewith.

 

3

SIGNATURE

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

 

    FORMA THERAPEUTICS HOLDINGS, INC.
Date: June 11, 2021     By:  

/s/ Jeannette Potts

      Jeannette Potts, Ph.D., J.D.
      SVP, General Counsel

 

4

Exhibit 99.1

 

LOGO

Forma Therapeutics Presents New Phase 1 Data on Etavopivat (formerly referred to as FT-4202) at 26th European Hematology Association Congress

Clinical results demonstrated durable improvement in hematologic and hemolytic markers, supporting the potential for improvement of red blood cell functional health in those with sickle cell disease

Initial results from an open-label extension cohort showed sustained hemoglobin increase of >1g/dL in 88% (7 of 8) of patients dosed for at least two and up to 12 weeks, as well as favorable tolerability profile

Improvement in markers of red blood cell functional health were observed, including data on measures of cell membrane integrity and systemic biomarkers of inflammation and coagulation

Forma to host webcast today at 8:00 a.m. ET to discuss etavopivat results presented at EHA

WATERTOWN, Mass. – June 11, 2021 – Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX) a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, today announced new data from its ongoing Phase 1 trial of etavopivat (formerly referred to as FT-4202) being presented at the 26th Annual European Hematology Association (EHA) 2021 Virtual Congress. The e-poster presentation includes initial data from the open-label extension (OLE) cohort showing etavopivat improved and sustained hematologic and hemolytic parameters for patients living with sickle cell disease (SCD) receiving 400 mg etavopivat once-daily for at least two weeks and up to 12 weeks. Also being presented are the unblinded results from the two multiple ascending dose (MAD) cohorts, which demonstrate once-daily dosing of 300 mg or 600 mg etavopivat for 14 days improved measures of sickle red blood cell (RBC) functional health, with effects persisting in some patients even after treatment discontinuation.

“Data presented today, including initial data from the OLE cohort, demonstrate patient responses improved with more than two weeks of dosing with etavopivat, including hemoglobin and markers of hemolysis, RBC functional health, and systemic inflammation and coagulation that together have the potential to reduce the incidence of vaso-occlusive crises with longer-term treatment,” said Patrick Kelly, MD, chief medical officer of Forma Therapeutics. “These results, along with the favorable tolerability profile we have observed, support our recent initiation of the Hibiscus Study – our Phase 2/3 trial in people living with SCD – and bring us one step closer to a potential new treatment option for those affected by SCD.”

Presentation Details

 

  •  

Abstract #EP1201: FT-4202 (Etavopivat) improves hematologic and hemolytic parameters in a phase 1 study of patients with sickle cell disease (Robert Clark Brown, M.D. PhD)

The e-poster presentation is available as of Friday, June 11, 2021, at 9:00 Central European Summer Time (CEST) and is accessible for on-demand viewing until Sunday, Aug. 15, 2021, on EHA’s virtual congress platform. The abstract and poster presentation are also available on Forma’s website.

Clinical Data Results

In the combined MAD1 (300 mg QD) and MAD2 (600 mg QD) cohorts, 73% (11 of 15) of patients achieved a hemoglobin increase of greater than 1g/dL over baseline; significant improvement in hematologic and hemolytic markers also include decreased absolute reticulocytes (100%, or 15 of 15), decreased LDH levels (73%, or 11 of 15) and decreased indirect bilirubin levels (93%, or 14 of 15). The osmoscan and oxygenscan results from 14 patients showed a statistically significant improvement.

Initial results as of May 24, 2021, in the OLE cohort for eight patients receiving once-daily etavopivat treatment (400 mg) for at least two weeks indicated a hemoglobin increase of greater than 1 g/dL in 88% (7 of 8), with a mean hemoglobin increase of 1.5 g/dL. Patient data indicated a durable response for those patients receiving treatment beyond two weeks for up to 12 weeks, with improved hematologic and hemolytic parameters. The improvement in RBC functional health extended beyond the 12-week treatment period; in one patient, improved sickle RBC deformability remained for up to four weeks after treatment discontinuation. These initial OLE data support the combined MAD cohort results and show that daily etavopivat treatment also significantly improved hematologic and hemolytic parameters.

The safety profile in the OLE cohort was consistent with underlying disease. Of note, two patients reported serious adverse events, including one vaso-occlusive crisis and acute chest syndrome, which was not considered related to treatment by the trial investigator. A deep-vein thrombosis (DVT) report was described as possibly related.

Additional results being presented at the conference are measures of RBC functional health, with analysis of RBC elongation and point-of-sickling data showing improvements in cell deformability, including durable changes for up to four weeks following treatment. The data show benefits beyond activation of the glycolytic pathway, including enhanced activity of enzymes involved in preventing and repairing oxidative damage and reduced levels of phosphatidyl serine (PS), a marker of membrane damage observed on the surface of sickle RBCs. Early data from the 12-week OLE cohort show favorable systemic biomarkers including lower levels of erythropoietin (EPO), reduced evidence of activation of coagulation (Prothrombin 1.2 and D-dimers) and decreased activation of innate immunity (TNF-a). These biomarkers suggest the potential for broader benefit to people living with sickle cell disease, including the potential to reduce vaso-occlusive crises.

Forma Webcast Today

Forma is hosting a webcast today at 8:00 a.m. ET to discuss these etavopivat results being presented at EHA. The webcast can be accessed in the “News & Investors” section of Forma’s website at www.formatherapeutics.com.

Ongoing Trials

The blinded, randomized, placebo-controlled portion of the ongoing Phase 1 trial is complete. People with SCD are now directly enrolling into the ongoing 12-week OLE cohort receiving 400 mg etavopivat daily.

Forma is currently enrolling adults and adolescents with SCD into the Hibiscus Study, a registrational Phase 2/3 randomized, placebo-controlled, double-blind, multicenter trial to further evaluate the safety and efficacy of etavopivat in this patient population. For more information, please visit https://hibiscusstudy.com/ or clinicaltrials.gov/NCT04624659.

About Sickle Cell Disease (SCD)

SCD is one of the most common single-gene disorders and is estimated to affect approximately 100,000 people in the United States, as well as approximately 30,000 in France, Germany, Italy, Spain and the United Kingdom. The National Institutes of Health (NIH) reports that prevalence is estimated at more than 20 million individuals globally. From 2010 to 2050, the annual number of newborns with SCD is expected to rise globally by approximately one-third.i Despite recent advances in treatment, most patients with SCD still suffer from pain crises, lifelong disability, significant morbidity and reduced quality of life.

About Etavopivat

Etavopivat is a novel investigational selective red blood cell (RBC) pyruvate kinase-R (PKR) activator designed to be a disease-modifying therapy for the treatment of sickle cell disease (SCD). Employing a multimodal approach, etavopivat is designed to work upstream by activating the RBCs’ natural PKR activity to decrease 2,3-DPG levels, which leads hemoglobin to hold on to oxygen molecules longer to reduce RBC sickling. The downstream activity of etavopivat is designed to increase ATP levels, the fuel that provides energy to cells, to improve RBC functional health and survival. Together, these effects are anticipated to increase hemoglobin levels and decrease painful vaso-occlusive crises. In preclinical safety studies, etavopivat did not inhibit aromatase activity or affect steroidogenesis, important biological processes responsible for sexual development. Etavopivat has been granted Fast Track, Rare Pediatric Disease and Orphan Drug designations from the U.S. Food and Drug Administration (FDA), and Orphan Drug Designation from the European Commission based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency for the treatment of patients with SCD.

About Forma Therapeutics

Forma Therapeutics is a clinical-stage biopharmaceutical company focused on the research, development and commercialization of novel therapeutics to transform the lives of patients with rare hematologic diseases and cancers. Our R&D engine combines deep biology insight, chemistry expertise and clinical development capabilities to create drug candidates with differentiated mechanisms of action focused on indications with high unmet need. Our work has generated a broad proprietary portfolio of programs with the potential to provide profound patient benefit. For more information, please visit www.FormaTherapeutics.com or follow us on Twitter @FORMAInc and LinkedIn.

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, express or implied statements regarding our beliefs and expectations regarding: initial results to date for the etavopivat open label extension cohort of our Phase 1 clinical trial; ; the therapeutic potential and clinical benefits and safety related to etavopivat; whether initial results from our clinical trials are predictive of final trial results or future clinical studies; and our planned presentation of data at the 2021 EHA Virtual Congress;. The

words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar 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, those risks and uncertainties related our ability to execute on our strategy; the therapeutic potential and safety of etavopivat; the timing and completion of our Phase 1 study of etavopivat and final audit and quality controlled verification of initial data and related analyses; the timing and success of our Phase 2/3 Hibiscus Study of etavopivat in SCD patients; positive results from initial data analyses may not be predictive of final results; risks related to our planned regulatory submissions and developments; and other risks identified in our SEC filings, including those risks discussed under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended March 31, 2021, as well as other risks detailed in our subsequent filings with the SEC. We caution you not to place undue reliance on any forward-looking statements, which speak only as of the date they are made. We disclaim any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this press release represent our views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. We explicitly disclaim any obligation to update any forward-looking statements.

Contacts

Media Contact:

Adam Silverstein, +1 917-697-9313

Porter Novelli

adam.silverstein@porternovelli.com

Investor Contact:

Mario Corso, +1 781-366-5726

Forma Therapeutics

mcorso@formatherapeutics.com

 

 

i 

Piel, F. B., Hay, S. I., Gupta, S., Weatherall, D. J., & Williams, T. N. (2013). Global burden of sickle cell anaemia in children under five, 2010-2015: Modelling based on demographics, excess mortality, and interventions. PLOS Medicine, 10(7). Retrieved from link.

SLIDE 1

European Hematology Association INVESTOR PRESENTATION JUNE 11, 2021 Exhibit 99.2

SLIDE 2

Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, express or implied statements regarding the company’s beliefs and expectations regarding its: business plans and objectives; future plans for etavopivat (FT-4202), FT-7051 and olutasidenib, including expectations regarding timing and success of the current ongoing clinical trials, therapeutic potential, clinical benefits and safety thereof, planned regulatory submissions, including a new drug application (NDA) for olutasidenib, and upcoming milestones for the company’s other product candidates; growth as a company; presentation of additional data at upcoming scientific conferences, and other preclinical data and potential data publications in 2021; the potential commercial and collaboration opportunities, including potential future collaborators and parties, as well as value and market, for our product candidates; uses and need of capital, expenses and other 2021 financial results currently or in the future, and the potential impact of COVID-19 on patient retention and enrollment, future operations, clinical trials or investigational new drug (IND) applications. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions 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, those risks and uncertainties associated with the following: the impact of the COVID-19 pandemic on the company’s business, operations, patient enrollment and retention , strategy, goals and anticipated milestones; the therapeutic potential of etavopivat, FT-7051, and olutasidenib, and the timing associated with the initiation or continuation of any trials and success of ongoing clinical trials of etavopivat and FT-7051; Forma’s ability to execute on its strategy; the submission and acceptance of an NDA for submission to the U.S. Food and Drug Administration (FDA) for olutasidenib; positive results from a clinical study may not necessarily be predictive of the results of future or ongoing clinical studies; any one or more of Forma’s product candidates may not be successfully developed and commercialized; regulatory developments in the United States and foreign countries; Forma’s ability to protect and maintain our intellectual property position; the impact of COVID-19 affecting countries or regions in which we have operations or do business, including potential negative impacts on our employees, customers, supply chain and production as well as global economies and financial markets; Forma’s ability to fund operations; Forma’s ability to identify satisfactory collaboration opportunities, as well as those risks and uncertainties set forth more fully under the caption "Risk Factors" in our quarterly report on form 10-Q for the period ended March 31, 2021 filed with the United States Securities and Exchange Commission (SEC) and subsequent filings with the SEC. Forma disclaims any obligation to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements. Any forward-looking statements contained in this presentation represent Forma’s views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Forma explicitly disclaims any obligation to update any forward-looking statements.

SLIDE 3

Meeting Agenda FORMA THERAPEUTICS OVERVIEW Frank D. Lee, President, CEO​ and Director Etavopivat Results Presentation Patrick Kelly M.D., Chief Medical Officer​ David Cook​, Ph.D. Chief Scientific Officer Question and Answer R. Clark Brown, M.D., Ph.D., Associate Professor Of Pediatrics, Emory University School Of Medicine Medical Director Of Sickle Cell At Scottish Rite, Aflac Cancer And Blood Disorders Center Of Children's Healthcare Of Atlanta Marilyn J. Telen, M.D., Wellcome Professor Of Medicine, Division Of Hematology​ Director, Duke Comprehensive Sickle Cell Center ​ ​ Meeting Summary and Close​ Frank D. Lee, President, CEO and Director​ 1 2 3 4

SLIDE 4

Frank Lee President, Chief Executive Officer, and Director

SLIDE 5

Transforming the lives of patients with rare hematologic diseases and cancers

SLIDE 6

Forma Therapeutics’ pipeline PROGRAM (TARGET) INDICATION DEVELOPMENT STAGE COMMERCIAL RIGHTS RECENT EVENTS PRECLINICAL PHASE 1 PHASE 2 PHASE 3 Etavopivat (PKR) Sickle Cell Disease Presented Phase 1 SCD data at EHA/ASH Ongoing Phase 1 SCD MAD/OLE Initiated Phase 2/3 pivotal trial (Hibiscus Study) Thalassemia FT-7051 (CBP/p300) mCRPC Cleared IND application Initiated Phase 1 trial Olutasidenib (IDH1m) AML NDA-enabling Phase 2 IA2 completed in R/R AML Presented Phase 2 AML data at ASCO 2021 Glioma Presented Phase 1 trial, 12-month data at ASCO 2020 FT-8225 (FASN) NASH CC-95775 (BET) NHL B1-1701963 (KRAS) Solid Tumors AML, acute myeloid leukemia; BET, bromodomain and extra-terminal; CBP/p300, BREN binding protein/p300; FASN, fatty acid synthase; IA2, interim analysis 2; IND, investigational new drug; IDH1m, isocitrate dehydrogenase 1 mutations; mCRPC, metastatic castration-resistant prostate cancer; NASH, nonalcoholic steatohepatitis, NHL, non-Hodgkin's lymphoma; PKR, pyruvate kinase-R

SLIDE 7

Potential timelines and milestones FPI, first patient in; IA, interim analysis; MAD, multiple ascending dose; NTD, non-transfusion dependent; OLE, open label extension; TD, transfusion-dependent PHASE 2: DOSE SELECTION PHASE 1 EHA Single dose SCD ASH MAD1 300mg EHA 12 week OLE Initial results ASCO Phase 1 data ETAVOPIVAT: SCD FT-7051: mCRPC PHASE 3: EFFICACY CONTINUATION IA#1 (12 weeks) Dose Selection FDA Type C IND MAD2 600mg FPI PHASE 1 SINGLE DOSE/MAD/OLE ETAVOPIVAT: THALASSEMIA (TD/NTD) PHASE 2 ASH Final OLE Results PEDIATRIC SCD 2020 2021 2022 ASCO GU AACR-NCI-EORTC

SLIDE 8

Significant unmet needs remain in SCD Prevalence ~100K SCD patients in the US ~1 in 365 Black Americans affected at birth 25-30yr Reduction in average life expectancy Symptoms May include anemia, inflammation, and painful vaso-occlusive crises ~55% Days with pain ↑Risk of Stroke Acute Chest Syndrome Renal failure Sources: Evaluate Report Sickle cell disease by country accessed February 03, 2020. Smith WR, et al. Ann Intern Med. 2008;148:94–101. Lanzkron S, et al. Pub Health Rep. 2013;128:110-116. Ballas, S.K. American Journal of Hematology DOI: 10.1002/ajh.21443. Centers for Disease Control and Prevention. Sickle cell disease (SCD) accessed May 4, 2021. Treatments ~50% >1 g/dL inc. in Hb or ~1 VOC improvement per yr (From 3 to 2 VOCs/yr) y

SLIDE 9

Etavopivat is a potential foundational, disease-modifying therapy Granted FDA Fast Track and Rare Pediatric, Orphan Drug designations Multi-modal MoA ↓2,3-DPG and ↑ATP Potential to improve both hemoglobin levels and VOCs Improves RBC health and functions important to metabolic health, adhesion, and survival Oral, once daily tablet-Low risk of drug-drug interactions; no aromatase inhibition properties; does not autoinduce its own metabolism Granted Fast Track, Rare Pediatrics and Orphan designations ✓ ✓ ✓ ✓ ✓

SLIDE 10

Patrick Kelly, M.D. SVP, Chief Medical Officer

SLIDE 11

Etavopivat Phase 1 Data Analysis as of May 2021

SLIDE 12

Etavopivat-mediated PKR Activation: Sickle RBC Health and Function Multimodal MOA: Increase Hb and Decrease VOC GLUCOSE Hb Deoxy-Hb PYRUVATE ATP ADP PEP 2,3-DPG PKR Etavopivat HbS polymerization RBC membrane integrity Anticipated Clinical Outcomes: Increased Hb levels Decreased vaso-occlusion HYPOTHESIS #2: PKR activation increases ATP, promoting RBC repair/health and reducing hemolysis HYPOTHESIS #1: PKR activation decreases 2,3-DPG, reducing HbS polymerization and sickling Hb=hemoglobin; deoxyHb=deoxygenated Hb ; PKR= pyruvate kinase-R; 2,3-DPG=2,3-diphosphoglycerate; ADP=adenosine diphosphate; ATP=adenosine triphosphate; PEP=phosphoenolpyruvate Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

SLIDE 13

Etavopivat Phase 1 Study: Design and Status Randomized, Placebo-controlled, Multi-center (NCT03815695) Healthy volunteers3 (N=90] Patients with SCD Single Ascending Dose (Completed) Randomization vs placebo 700 mg 300 mg once daily Single Dose4 (Completed, N=7) Randomization vs placebo Multiple Ascending Dose (Completed, N=20) Etavopivat vs placebo, 2 weeks of treatment 600 mg once daily 700 mg 400 mg 200 mg 100 mg BID Multiple Ascending Dose (Completed) Randomization vs placebo, 2 weeks of treatment 200 mg BID 300 mg BID 1000 mg 400 mg QD Open-label Extension (Ongoing, N = up to 20 ) Etavopivat, 12 weeks of treatment 400 mg once daily EHA 2021 Patients with SCD treated with etavopivat (300 mg and 600 mg) once daily x 2 weeks (data as of May 10, 2021) Patients with SCD treated with etavopivat 400 mg once daily x 12 week; initial results* (data as of May 24, 2021) SCD=sickle cell disease Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202 * Initial results for patients who received etavopivat 400 mg once daily for at least 2 weeks: patients had a median of 10 weeks (mean of 8 weeks) of etavopivat treatment

SLIDE 14

Parameter, Mean (range) or n (%) Etavopivat or Placebo once daily, 2 weeks Etavopivat once daily, 12 weeks 300 mg (N=10) 600 mg (N=10) 400 mg (N=10) Age, years 28.5 (19, 43) 24.0 (17, 64) 26.5 (17, 41) Male 3 (30%) 3 (30%) 3 (30%) Genotype HbSS  9 (90%) 8 (80%) 10 (100%) HbSβ+-thalassemia 1 (10%) 1 (10%) 0 HbSC 0 1 (10%) 0 HU therapy 7 (70%) 9 (90%) 10 (100%) Hb, g/dL 8.7 (6.9, 10.1) 8.6 (7.3, 10.2) 8.8 (7.7, 10.0) % HbS 82.0 (67.0, 92.9)  83.5 (78.2, 92.7) 81.8 (72.6, 92.7)# % HbF 11.5 (3.5, 20.1)  12.0 (4.4, 19.2) 13.6 (4.4, 23.0)# MCV, fL 107.1 (75.0, 131.5) 108.2 (68.5, 129.6) 110.4 (91.0, 122.7) ARC, 109/L 249.1 (125.6, 329.3) 250.6 (29.4, 366.0) 246.6 (78.3, 363.2) Indirect bilirubin, mg/dL 3.05 (0.5, 10.5) 2.27 (0.7, 5.0) 2.24 (0.9, 5.2) LDH, U/L 398.2 (180, 699) 419.8 (251, 683) 424.6 (186, 683) % F cells 41.7 (16.4, 67.2) 43.3 (13.3, 64.8) 54.9 (22.3, 76.9) Etavopivat Phase 1 Study: Patient Baseline Characteristics ARC=absolute reticulocyte count; Hb=hemoglobin; HbF=fetal hemoglobin; HbS=sickle hemoglobin; HU=hydroxyurea; LDH=Lactate dehydrogenase; MCV= mean corpuscular volume Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. #n=8

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Etavopivat 300 mg and 600 mg Once Daily for 2 Weeks: Comparable Decrease in 2,3-DPG and Increase in ATP Dose-proportional PK and comparable PD responses (↓ 2,3-DPG and ↑ ATP) with etavopivat 600 mg or 300 mg once daily for 2 weeks Confirms prior studies in healthy volunteers predicting doses ≥ 400 mg once daily would maximize PD Overlapping PD results support combined analyses of the 300 mg and 600 mg dose cohorts Results support etavopivat 400 mg once daily as the maximum dose in the Phase 2/3 pivotal trial (the Hibiscus Study) PK=Pharmacokinetics; PD=Pharmacodynamics Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Hibiscus Study (NCT04624659) Data as of May 10, 2021 ATP 2,3-DPG Etavopivat

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Parameters Placebo (N=4) Etavopivat 300 mg Once daily, 2 weeks (N=8) Etavopivat 600 mg Once daily, 2 weeks (N=8) AE, n (%) Any AE 1 (25.0) 7 (87.5) 6 (75.0)​ Related to study drug 0 2 (25.0) 0 Any SAE 0 0   1 (12.5) Related to study drug 0 0 0 AEs by severity Grade 1 Grade 2 Grade 3 Grade 4 3 2 1 1 6 7 0 0 7 7 1 0 Etavopivat Once Daily for 2 Weeks was Well-tolerated: Comparable Safety Profile with 300 mg or 600 mg Once Daily AE=adverse event; SAE=serious AE Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Hibiscus Study (NCT04624659) Favorable tolerability profile, most common AEs (≥ 3 pts): Sickle cell anemia pain events (n=5), headache (n=4), and nausea (n=3) Etavopivat was well-tolerated up to 600 mg once daily, which is 150% of the Hibiscus Study maximum dose Data as of May 10, 2021

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Etavopivat 300 mg or 600 mg Once Daily for 2 Weeks Significantly Improves Hematologic and Hemolytic Parameters EOT=end of treatment; Hb=hemoglobin; LDH=lactate dehydrogenase Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 10, 2021 In patients treated with etavopivat and evaluable for response (n=15): 73% (11/15) achieved Hb ≥ 1 g/dL over baseline at EOT (mean ↑ 1.2 g/dL; p<0.002) 100% (15/15) had ↓ absolute reticulocytes relative to baseline at EOT (mean ↓ 47%; p<0.001) 73% (11/15) had ↓ LDH levels over baseline at EOT (mean ↓ 19%; p<0.07) 93% (14/15) had ↓ indirect bilirubin levels over baseline at EOT (mean ↓ 38%; p<0.002)

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Etavopivat Once Daily up to 12 Weeks was Well-tolerated: Safety Profile Consistent with Underlying Disease AE, n (%) Etavopivat 400 mg once daily up to 12 weeks1 AE, n (%) All Grades (≥ 10%) N=8 Grade ≥ 3 N=8 Acute chest syndrome (ACS) 1 (12.5) 1 (12.5) Blood CPK abnormal 1 (12.5) 1 (12.5) Deep Vein Thrombosis (DVT) 1 (12.5) 1 (12.5) Fatigue 1 (12.5) 0 Headache 1 (12.5) 0 Lymphadenopathy 1 (12.5) 0 Menorrhagia 1 (12.5) 0 Muscle strain 1 (12.5) 0 Neutropenia 1 (12.5) 0 Peripheral swelling 1 (12.5) 0 Priapism 1 (12.5) 0 Sickle cell anemia with crisis (VOC) 1 (12.5) 1 (12.5) Serious AEs: 1 patient (unrelated): ACS and VOC after EOT, precipitated by upper respiratory infection symptoms (non-COVID) 1 patient (possibly related): left femoral vein DVT on day 14 of treatment 1AEs in patients who received etavopivat 400 mg once daily for at least 2 weeks (median 10 weeks; mean 8 weeks) AE=adverse event; EOT=end of treatment Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 24, 2021

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Etavopivat 400 mg Once Daily up to 12 Weeks: Improved and Sustained Hemoglobin Increase Responder Parameter N=8 Maximal Hb increase, mean (SD), g/dL  1.5 (0.4) Hb increase > 1 g/dL, n (%) 7 (88) Maximal Hb increase in subjects with > 1 g/dL response, mean (SD), g/dL  1.6 (0.3) Hemoglobin Hb=hemoglobin; BL=baseline; Wk=week Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Patients who received etavopivat 400 mg once daily for at least 2 weeks: patients had a median of 10 weeks (mean of 8 weeks) of etavopivat treatment Data as of May 24, 2021

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Etavopivat 400 mg Once Daily up to 12 Weeks: Decreased and Sustained RBC Turnover and Hemolysis LDH=lactate dehydrogenase; BL=baseline; wk=week Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 24, 2021 Reticulocytes LDH Bilirubin Trend towards normalization of reticulocytes, bilirubin and LDH by 12 weeks Patients who received etavopivat 400 mg once daily for at least 2 weeks: patients had a median of 10 weeks (mean of 8 weeks) of etavopivat treatment

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Etavopivat 400 Mg Once Daily for 12 Weeks: Reduction in Systemic Markers of Sickle Cell Pathophysiology Lab Test Normal range Patients (n) Baseline Median % Maximum Change (range) P-value Tissue hypoxia Erythropoietin 2.6 – 18.5 mIU/mL 4 140.3 (106.7, 157.1) -42.3 (-66.6, -7.3) 0.1250 Hypercoagulability Prothrombin 1.2 87 – 325 pmol/L 7 617 (386, 4900) -61.0 (-86.5, 10.2) 0.0313 D-dimer < 0.50 mcg/mL 6 3.56 (2.08, 5.9) -51.9 (-94.3, 25.5) 0.0625 Inflammation TNF-a 0.56-1.40 pg/mL 7 1.34 (0.79, 2.2) -26.1 (-69.4, 0.9) 0.0313 Patients receiving etavopivat 400 mg daily for up to 12 weeks were assessed for systemic markers of sickle cell pathophysiology including: Intravascular hemolysis: Indirect bilirubin and LDH Tissue hypoxia: erythropoietin levels Hypercoagulability: Prothrombin 1.2, TAT complexes and D-dimer Inflammation: ferritin, CRP, TNF-a, IL-1b, IL-8 and IL-6 Data as of June 6, 2021

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EImax Pre EOT EOS P50 29.7 25.2 32 Pre EOT EOS POS EImax 40.6 30.7 40.8 0.32 0.52 0.49 Pre EOT EOS EImax 0.42 0.54 0.52 O2 Affinity Curve Osmoscan Healthy RBC: SCD RBC (Pre-dose): SCD RBC EOT (Day 15): SCD RBC EOS (Day 21): Oxygenscan POS EImax Patient with SCD before and after 2 wks of etavopivat and after a 1-wk washout EOT = end of treatment; EOS = end of study; POS = point of sickling Etavopivat Improved the Functional Health of Sickle RBCs Sickle RBCs from patients who received etavopivat for 2 wks had an assessment of functional health by O2 affinity, O2 gradient, or an osmotic gradient A representative analysis from 1 patient performed pre-treatment, at EOT, and up to 1 wk after completion of etavopivat treatment (EOS) is shown Collectively, results from 14 patients analyzed show that etavopivat-treated sickle RBCs have significantly increased Hb-O2 affinity (p=0.0001), significant shift in the POS (p=0.004) and significantly improved deformability (EImax) by oxygenscan (p=0.025) or osmoscan (p=0.037)

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Improvement in Sickle RBC Deformability May Persist after Etavopivat Treatment Discontinuation Oxygenscans performed at the indicated timepoints showed: Improved RBC deformability (EImax) after 2 weeks of etavopivat at both doses EImax returning to pre-treatment level during WO between etavopivat treatments Improved RBC deformability maintained for at least 4 weeks after WO of etavopivat 400 mg once daily Etavopivat-treated patient: 600 mg once daily for 2 wks, followed by 3 wks WO then etavopivat 400 mg once daily for 12 wks, followed by 4 wks WO WO=washout; wk=week Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. Data as of May 24, 2021

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Etavopivat Improved RBC Functions Important for Metabolic Health, Adhesion, and Survival PS Expression n=11 n=13 n=13 n=8 A: B: C: D: GSH Reductase Activity SOD Activity PKR Activity RBCs from patients with SCD treated with etavopivat 300 mg or 600 mg QD for 2 wks showed: ↑ PKR activity over baseline, comparable for 300 mg and 600 mg dose cohorts (A) ↑ in RBC antioxidant capacity and improved RBC redox potential (B, C) ↓ PS expression on the sickle RBC membrane suggesting improved membrane repair (D) PKR = RBC Pyruvate Kinase; SOD = super-oxide dismutase; GSH = glutathione; PS = phosphatidyl serine Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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David Cook, Ph.D. SVP, Chief Scientific Officer

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Etavopivat MOA and Novel Biology from Phase 1 Data

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Etavopivat: Results Supporting Improved RBC Functional Health 1 2 3 4 5 6 PKR= pyruvate kinase-R; 2,3-DPG=2,3-diphosphoglycerate; ATP=adenosine triphosphate; PS=phosphatidyl serine 7 Reduced potential for vascular activation and vaso-occlusion Reduced membrane damage Reduced protein, membrane & blood vessel damage (vasculopathy) Increased ability to transit small vessels Increased RBC lifespan and reduced inflammation Increased RBC energy reserves Reduced RBC sickling  Decreased Levels of 2,3-DPG   Increased Levels of ATP   Decreased Hemolysis   Improved RBC Hydration and Deformability   Decreased PS on the RBC Membrane   Increased Antioxidant Enzyme Activity Decreased procoagulant & proinflammatory biomarkers

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Sickle Cell Disease, although Driven by a Single Mutation, is Complex and Multifactorial Sickling Hemolysis Free Heme Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Activation of Innate Immune Pathways Vaso-occlusion Activation of Vascular Epithelium and Vaso-constriction Ischemia Reperfusion Injury modified from Gladwin, Kato, Novelli 2021

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Decreased 2,3-DPG: Reduced RBC Sickling Etavopivat consistently decreases 2,3-DPG + DPG / −O2 − DPG / +O2 Decreased 2,3-DPG increases oxygen affinity and reduces polymerization and sickling Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 1 1 1 2,3-DPG=2,3-diphosphoglycerate Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Increased ATP: Increased RBC Energy Charge Etavopivat consistently increases ATP and PKR activity ↑ ATP essential for membrane repair, ionic homeostasis, hydration and deformability Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 2 2 2 PKR Activity ATP ATP=adenosine triphosphate; PKR=pyruvate kinase-R Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Decreased Hemolysis: Increased RBC lifespan and Reduced Inflammation Etavopivat ↑ Hb and ↓ reticulocytes demonstrating increased RBC lifespan Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction Etavopivat ↓ LDH and ↓ bilirubin demonstrating decreased hemolysis 3 3 3 LDH=lactate dehydrogenase Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Improved RBC Deformability and Hydration: Increased Ability to Transit Small Vessels Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 4 4 Etavopivat results in higher baseline deformability as measured by Oxygenscan Deformability (EI units) Oxygen Pressure (mmHg) Deformability is durable up to 4 weeks after 12-weeks treatment Deformability (EI units) Etavopivat improves ability to maintain ionic gradients and intracellular hydration as measured by Osmoscan Deformability (EI units) Osmolality (mOsm/kg) Enabled by ATP and improved anti-oxidant activity 4 ATP=adenosine triphosphate Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Decreased PS: Reduced Membrane Damage Repeated sickling results in PS on the outer RBC membrane Etavopivat decreases PS expression on RBC outer membrane Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 5 5 PS Expression PS ATP ADP Flippase PS accelerates RBC clearance by the macrophages in spleen and liver ATP repairs this damage by activating flippase, which flips PS back to the inner RBC membrane 5 PS=phosphatidyl serine; ATP=adenosine triphosphate; ADP=adenosine diphosphate; Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Etavopivat increases activity of SOD and GSH Reductase Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction ↑ SOD and GSH reductase aid in elimination of toxic reactive oxygen species from sickle RBC This reduces damage to membranes and proteins 6 6 GSH Reductase SOD 02 SOD H202 + H20 catalase 02 + H20 02 + H20 superoxide GSH GSSG GSH Reductase 6 Increased Anti-oxidant Enzyme Activity: Reduced Protein, Membrane and Blood Vessel Damage SOD = super-oxide dismutase; GSH = glutathione Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202].

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Decreased Pro-inflammatory and Pro-coagulant Markers: Reduced Potential for Vascular Activation and Vaso-occlusion Pain Crisis Stroke Infection Organ Damage Early Death HbS Polymerization Innate Immune Activation Vaso-occlusion Vascular Activation and Vaso-constriction 7 7 7 ATP=adenosine triphosphate Brown RC, et al. Presented at: EHA 2021 Virtual Meeting; Jun 9-17, 2021 [E-Poster EP1202]. 7 Cytokines (e.g. TNF-a) activate blood coagulation and adhesins on neutrophils, platelets and vascular endothelium In narrow vessels, sickled RBCs bind these activated cells and cause vaso-occlusion

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Etavopivat-mediated activation of glycolysis results in: Reduced RBC sickling – the key to all downstream pathology Decreased hemolysis – a driver of inflammation & vascular activation Improved RBC deformability & hydration – reducing vaso-occulsion Reduced membrane damage – reducing RBC adhesion and clearance Protection from reactive oxygen species – protects both proteins and membranes Reduced pro-inflammatory and pro-coagulant biomarkers – demonstrating systemic effects of etavopivat These data suggest etavopivat may improve the overall functional health of sickle RBCs and reduce the risk of vaso-occlusive events, thus altering the pathophysiology of SCD Etavopivat-mediated PKR Activation Demonstrates Potential to Improve RBC Health via Multimodal MOA

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Q&A

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Frank Lee President, Chief Executive Officer, and Director

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Summary – Etavopivat Phase I Results Support Hibiscus Study Design And Potential as Foundational Therapy in SCD Rigorous Phase I study Etavopivat once daily  A favorable tolerability profile in patients with SCD - supporting a safety margin for maximum dose selected for Hibiscus Study ( Phase 2/3 ) Initial results from the open-label 12-week dose cohort indicate a sustained hemoglobin increase (>1 g/dL) in 88% of patients for up to 12 weeks with a trend toward normalization in markers of hemolysis Improved sickle RBC deformability sustained for up to 4 weeks after treatment discontinuation Improved RBC functions important for metabolic health, adhesion, and survival Improved systemic markers of SCD pathophysiology beyond metabolic pathway

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Thank you to our patients, caregivers, and investigators