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):

October 7, 2019

 

SYNDAX PHARMACEUTICALS, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Registrant’s telephone number, including area code: (781) 419-1400

 

(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 (see General Instruction A.2. below):

Securities registered or to be registered pursuant to Section 12(b) of the Act.

 

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.  ☑

 

 

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Syndax Pharmaceuticals, Inc., a Delaware corporation (“we,” “us,” or the “Company”) announces today that ECOG-ACRIN Cancer Research Group, the sponsor of our Phase 3 registration trial of entinostat plus exemestane in advanced hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+, HER2-) breast cancer, E2112, notified us in advance of their October 24 – 26 biannual group meeting that the trial has passed its fifth and final interim overall survival (OS) analysis.  The E2112 trial design was informed by the Phase 2b ENCORE 301 trial, the results of which led to entinostat’s Breakthrough Therapy designation in HR+, HER2- breast cancer, in which patients receiving the entinostat/exemestane combination demonstrated a strong OS benefit.  

The trial will now continue until the final OS analysis, which will happen when 410 deaths from among the 608 patients enrolled have occurred.  Based upon our modeling of the assumed event rate, we expect this final analysis to occur in the second quarter of 2020.  We have included in this filing a revised corporate presentation containing the update to the E2112 trial.

A copy of the above referenced presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K. This information, including the information contained in the presentation furnished as Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not incorporated by reference into any of the Company’s filings, whether made before or after the date hereof, regardless of any general incorporation language in any such filing.

(d) Exhibits.

 

 

 

 

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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.

 

Dated: October 7, 2019

 

Corporate presentation | October 2019 Determined to realize a future in which people with cancer live longer and better than ever before

Forward-looking statements disclosure This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "may," "will," "expect," "plan," "anticipate" and similar expressions (as well as other words or expressions referencing future events or circumstances) are intended to identify forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding future operations, financial results and the financial condition of Syndax Pharmaceuticals, Inc. (“Syndax” or the “Company”), including financial position, strategy and plans, the progress, timing, clinical development and scope of clinical trials and the reporting of clinical data for Syndax’s product candidates, and Syndax’s expectations for liquidity and future operations, are forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical site activation rates or clinical trial enrollment rates that are lower than expected, changes in expected or existing competition, failure of our collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. Moreover, Syndax operates in a very competitive and rapidly changing environment. Other factors that may cause our actual results to differ from current expectations are discussed in Syndax’s filings with the U.S. Securities and Exchange Commission, including the “Risk Factors” sections contained therein. New risks emerge from time to time. It is not possible for Syndax’s management to predict all risks, nor can Syndax assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statement. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied. Except as required by law, neither Syndax nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. Syndax undertakes no obligation to update publicly any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in Syndax’s expectations.

Syndax Current Pipeline Entinostat Class I HDAC inhibitor Preclin. Phase I Phase II Phase III Indication(s) Sponsor HR+, HER2- mBC NCI/Syndax NSCLC Syndax Melanoma Syndax SNDX-6352 CSF-1R mAB Preclin. Phase I Phase II Phase III Indication(s) Sponsor Chronic GVHD Syndax SNDX-5613 Menin inhibitor Preclin. Phase I Phase II Phase III Indication(s) Sponsor MLLr leukemias, NPM1c AML Syndax E2112: Entinostat + exemestane Entinostat + pembrolizumab* Entinostat + pembrolizumab* SNDX-6352 monotherapy SNDX-5613 monotherapy * Development on hold pending positive E2112 OS trial results

Oral, Class I HDAC in HR+ mBC Positive OS data possible 2Q20 NDA filing anticipated 2H20 Efficacy in CDK4,6 treated patients Blockbuster potential 2019: Portfolio prioritization to drive value HR+ mBC – hormone receptor positive metastatic breast cancer; MLL – mixed lineage leukemia; AML – acute myeloid leukemia; ALL – acute lymphoblastic leukemia Oral, Menin inhibitor Blocks activity of MLL-fusion proteins IND cleared; initial data expected 2020 Benefit expected in high need AML, ALL Blockbuster potential Entinostat + exemestane Potential near-term FDA approval SNDX-5613 BTD Targeted therapy provides fast to market opportunity

SNDX-5613 Menin inhibitor Leukemias Entinostat Breast Cancer Immuno- oncology New molecules Oncology SNDX-6352 anti-CSF1R Ab Immuno- oncology GvHD Immuno- oncology

Entinostat re-sensitizes cancer cells ERα+ Breast Cancer Acquires Hormone Resistance estrogen dependent estrogen drives tumor growth sensitive to hormone therapy acquired resistance to hormone therapy ERa+ breast cancer cell + entinostat estrogen independent growth factors drive tumor growth resistant to hormone therapy ERa+ breast cancer cell

Phase 2 trial resulted in breakthrough therapy designation Overall Survival EE = exemestane plus entinostat EP = exemestane plus placebo Placebo 0/0 1/3 5/18 8/35 12/47 13/60 4/66 Entinostat 0/1 2/9 3/21 9/43 4/49 5/55 4/64 EE: median OS 28.1 months EP: median OS 19.8 months Hazard Ratio 0.59 (95% CI: 0.36, 0.97) P=0.036 (2-sided) ; P=0.018 (1-sided) 1.00 0.75 0.50 0.25 0.00 0 6 12 24 18 30 36 42 Survival probability Source: Yardley, Denise A., et al. Journal of Clinical Oncology 31.17 (2013): 2128-2135 Progression-free Survival Placebo 31/66 13/33 4/20 5/16 2/11 4/9 0/5 1/4 1/3 1/1 0/0 0/0 0/0 Entinostat 15/64 14/45 11/29 3/17 4/14 2/10 0/8 0/8 3/8 2/5 0/1 0/1 0/1 Months 1.00 0.75 0.50 0.25 0.00 0 2 4 6 8 18 20 22 24 26 16 14 12 10 Progression probability EE: median PFS 4.3 months EP: median PFS 2.3 months Hazard ratio 0.73 (95% CI: 0.50, 1.07) P=0.055 (1-sided) Months (#events / #at risk) (#events / #at risk)

Phase 3 E2112: Focused on overall survival 4Q18: Accrual completed (n=608), PFS and interim OS analyses shared 4Q19: Passed final interim OS futility 2Q20: Final OS analysis Expect to file NDA ~6 months after positive OS data E2112 Trial Milestones E2112: Exemestane +/- entinostat Randomized, blinded Exemestane + entinostat (n=300) Exemestane + placebo (n=300) Primary endpoint: OS BTD A positive OS result allows filing for full regulatory approval Advanced HR+ HER2- BC following SOC progression

Source: DataMonitor 2016 Breast cancer: HR+/HER2- Disease Coverage Report Blockbuster potential as 2nd/3rd line agent Anastrozole or letrazole +/- CDK4,6 inhibitor Capecitabine, gemcitabine, eribulin Leading treatment options – HR+, HER2- advanced breast cancer 1st line hormone Tx Anastrazole, Faslodex +/- CDK4,6 inhibitor or Afinitor-exemestane Entinostat-exemestane target population 34,000 pts 2nd/3rd/4th line hormone Tx Chemo-Tx

SNDX-5613 Menin inhibitor Leukemias Entinostat Breast Cancer Immuno- oncology New molecules Oncology SNDX-6352 anti-CSF1R Ab Immuno- oncology GvHD

Strong target validation Precise patient selection Big effect in small studies Molecular markers of disease status Rapid regulatory path Advantages SNDX-5613 targets novel fusion protein: fusion proteins proven to be good candidates for targeted therapies BCR-ABL NTRK Fusions EML4-ALK RET Fusions LOXO-292 (Loxo/Lilly) BLU-667 (Blueprint) Therapies targeting fusion proteins

MLL1 fusion partner recruits oncogenic factors to transcription site1 Menin is a scaffold protein involved in gene transcription MLL1 N-terminus binds w/in conserved pocket on Menin MLL1 Transformations Menin In MLLr, leukemic transformation is highly dependent on the Menin-MLL interaction Inhibitor MENIN MLL peptide Conserved N-terminus Menin Binding Motif H2N H2N Break Point Region MLL-rearrangement (KMT2A fusion) H2N CO2H Fusion partner MLL1 (KMT2A) protein CO2H CO2H Source: Yokoyama A, Cell. 2005 Oct 21;123(2):207-18; Caslini C, Cancer Res. 2007 Aug 1;67(15):7275-83. SNDX-5613 designed to block site of interaction

Binding of Menin to MLL1 leads to upregulation of HOX gene transcription and leukemia in MLLr AML and MLLr ALL Adopted from: Uckelmann HJ, et al. Presented at ASH Annual Meeting, 2018. MLLr AML or MLLr ALL Inhibition with SNDX-5613 Menin ON Leukemia Differentiation OFF SNDX-5613 HOX MLL1 Fusion Menin HOX DOT1L CDK9 P-TEFb TIP60 CBX8 MLL1 Fusion DOT1L CDK9 P-TEFb TIP60 CBX8

SNDX-469 shows profound, single agent treatment benefit in multiple models Menin-MLL inhibition significantly prolongs survival in MLLr xenograft models MLLr Cell Line Xenograft (MV4;11) (SNDX-469) Patient Derived Xenograft (PDX) MLL-AF4 (SNDX-469) 28d Tx (28d) 0 20 40 60 0 20 40 60 80 100 Treatment Period Day of Study Percent Survival Vehicle 15 mg/kg BID 30 mg/kg BID 60 mg/kg BID 80 Vehicle 60 mpk 30 mpk 25% 50% 100% 75% 0% EFS Probability Days Post Treatment Initiation 0 21 105 168 42 63 84 126 147 189 Source: Kristov, A., 2018 American Association for Cancer Research annual meeting

SNDX-5613 potentially effective in MLLr – ALL; distinct molecular subtype of ALL conferring a worse prognosis Pediatric ALL: 75%-90% MLLr ALL: ~50% for infants and ~60% >1 yr Adopted from: Shah, B. and Nasello, D. Jan 2019; NCCN conference and meetings: Update on Management of Acute Lymphoblastic Leukemia. 5-year survival WW incidence ~1,000/yr 10-15% ALL, 80% infant ALL

SNDX-5613 poised to target MLLr and NPM1 classes of AML; distinct subsets representing ~34% of AML Adopted from: Dohner, H. et al. Blood, 2017; 129(4):424-447 MLLr AML (4 - 10% AML) ~3,000 patients / year NPM1 AML (30% AML) ~20,000 patients / year WW Incidence AML 5 yr survival 5% - 55%

NPM1 transfected mice showed profound single agent survival benefit with SNDX-469 in multiple PDX models NPM1c; FLT3 ITD; PHF6 mice (treated with SNDX-469 or vehicle) Preclinical models of NPM1 AML reveal profound single agent activity of Menin inhibition NPM1 mutation is the most frequent molecular alteration in AML Like MLLr, NPM1 AML depends on genes known to be sensitive to Menin-MLL interaction Standard AML screening identifies NPM1 mutation today % Mice Alive Days Post-transplant Early stage MLL inhibitor Vehicle 150 mg/kg/day 0 60 120 180 240 300 360 0 20 40 60 80 100 Source: Kühn MW, Cancer Discov. 2016 Oct;6(10):1166-1181; Kristov, A., 2018 American Association for Cancer Research annual meeting

PEDS ADULTS SNDX-5613: potential best-in-class, targeted, oral agent with single agent activity and fast to market potential MLLr ALL NPM1 AML MLLr AML Phase 1/2 trial population: MLLr adult, MLLr peds, NPM1 mut AML IND cleared; AUGMENT program init. Initial data expected in 2020 MLLr and NPM1 identified today with standard screening protocols No approved therapies targeting MLLr or NPM1 acute leukemias $$B commercial opportunity Defined fast to market pathway

AUGMENT clinical program: testing oral Menin inhibitor, SNDX-5613, in patients with acute leukemia Adult NPM1 mut AML Adult MLL-r ALL Adult MLL-r AML Enrolling R/R acute leukemias* Accel. titration into 3+3 design 28 day cycle Primary endpoint: CR Rate (CR + CRh^) * Unselected population; ^ CR = Complete response, CRh = Complete response with partial hematologic recovery; MLL-r – mixed lineage leukemia rearranged; NPM = nucleophosmin Phase 1: Dose escalation Phase 2: Expansion Endpoints: Safety, PK, RP2D

SNDX-5613 Menin inhibitor Leukemias Entinostat Breast Cancer Immuno- oncology New molecules Oncology SNDX-6352 anti-CSF1R Ab Immuno- oncology GvHD

Update on SNDX-6352: pursuing novel indication High affinity, IgG4 (KD = 4-8 pM) Chronic graft versus host disease (cGVHD) study initiated Expect phase 1 dose escalation results in 2H20 Ascending dose trials: Identified RP2D in combo with IMFINZI® (durvalumab, AZ) Monotherapy (solid tumors) ongoing SNDX-6352 Ligand binding Dimerisation ATP binding Kinase insert Kinase domain P P P P P P P CSF-1 Receptor CSF-1R – colony stimulating factor -1 receptor; RP2D recommended Phase 2 dose. Source : Ordentlich, P. et al SITC 2016.

Ticker SNDX (NASDAQ) As of June 30, 2019 Cash and short-term investments $98.4 million $80.5 million Shares Outstanding* 22.7 million 31.6 million 2019 3Q and full year Operating Expense Guidance 3Q 2019 2019 Research and Development $11 – 12 M $45 - 47 M Total Operating Expenses^ $15 – 16 M $60 – 63 M 2Q 2019 financial highlights and 3Q, full-year 2019 guidance * Includes 27.1 million common shares and pre-funded warrants to purchase 4.5 million common shares ^ Includes $1.5 and $6 million non-cash stock compensation expense for 3Q 2019 and for 2019, respectively

ENTINOSTAT (Class 1 specific HDAC inhibitor) 4Q19 1Q20 2Q20 2H20 E2112 – Final OS analysis expected Key upcoming milestones SNDX-6352 (anti-CSF-1R mAB) 4Q19 1Q20 2Q20 2H20 Results from Phase 1 chronic GVHD trial SNDX-5613 (Menin inhibitor) 4Q19 1Q20 2Q20 2H20 Results from phase 1 portion of AUGMENT (in R/R acute leukemias)

Oral, Class I HDAC in HR+ mBC Positive OS data possible 2Q20 NDA filing anticipated 2H20 Efficacy in CDK4,6 treated patients Blockbuster potential 2019: Portfolio prioritization to drive value HR+ mBC – hormone receptor positive metastatic breast cancer; MLL – mixed lineage leukemia; AML – acute myeloid leukemia; ALL – acute lymphoblastic leukemia Oral, Menin inhibitor Blocks activity of MLL-fusion proteins IND cleared; initial data expected 2020 Benefit expected in high need AML, ALL Blockbuster potential Entinostat + exemestane Potential near-term FDA approval SNDX-5613 BTD Targeted therapy provides fast to market opportunity

Thank you. Questions?