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): December 9, 2024
(Exact name of registrant as specified in its charter)
| (State or other jurisdiction of incorporation) | (Commission File Number) | (IRS Employer ID Number) | ||||||||||||
(Address of principal executive offices) (Zip Code)
(510 ) 970-6000
(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 | Trading Symbol(s) | Name of each exchange on which registered | ||||||||||||
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.
As previously reported in the October 4, 2024 Form 8-K of Sangamo Therapeutics, Inc., or Sangamo, Sangamo filed a Certificate of Amendment of the Restated Certificate of Incorporation with the Delaware Secretary of State on June 4, 2024, which increased the number of authorized shares of the Common Stock from 640,000,000 to 960,000,000 shares (the “Common Stock Increase Amendment”). At Sangamo’s 2024 annual meeting of stockholders held on June 4, 2024 (the “2024 Annual Meeting”), the holders of a majority of the outstanding shares of Common Stock of Sangamo approved the Common Stock Increase Amendment.
In connection with the 2024 Annual Meeting, Sangamo filed a proxy statement on Schedule 14A (the “Proxy Statement”) on April 19, 2024. The Proxy Statement described the voting threshold needed to approve the Common Stock Increase Amendment as requiring an affirmative vote of a majority of all votes cast at the 2024 Annual Meeting. Sangamo believes that the Proxy Statement accurately described the vote required to adopt the Common Stock Increase Amendment under a recently enacted provision of the Delaware General Corporation Law (the “DGCL”) (Section 242(d)(2)), which became effective on August 1, 2023.
On June 3, 2024, the law firms of Pomerantz LLP and Fields Kupka & Shukurov LLP filed a stockholder class action complaint against Sangamo and Sangamo’s board of directors in the Delaware Court of Chancery (“Court of Chancery”) on behalf of one purported stockholder of Sangamo. Among other matters, the complaint alleged that because the Proxy Statement had specified that a majority-of-votes-cast voting standard was required for the approval of the Common Stock Increase Amendment, rather than a majority-of-outstanding-shares voting standard, the Common Stock Increase Amendment and any issuances of Common Stock pursuant thereto were and are not validly authorized, despite the fact that both a majority of the votes cast at the 2024 Annual Meeting and a majority of the outstanding shares of Common Stock as of the record date for the 2024 Annual Meeting voted in favor of the Common Stock Increase Amendment. On July 8, 2024, Sangamo and Sangamo’s board of directors filed a motion to dismiss the stockholder class action complaint.
To resolve any uncertainty with respect to the validity of the Common Stock Increase Amendment, on August 29, 2024, Sangamo filed an application in the Court of Chancery under Section 205 of the DGCL, seeking to validate the effectiveness of the Common Stock Increase Amendment (the “Section 205 Application”). Section 205 of the DGCL permits the Court of Chancery, in its discretion, to ratify and validate potentially defective corporate acts. As previously reported, the Court of Chancery scheduled a hearing on Sangamo’s Section 205 Application for December 12, 2024.
On November 27, 2024, the Court of Chancery issued an opinion in Salama v. Simon, C.A. No. 2024-1124-JTL (Del. Ch.), which confirmed that Sangamo’s Proxy Statement accurately described the vote required to adopt the Common Stock Increase Amendment under Section 242(d)(2). As a result of the Court of Chancery’s opinion, Sangamo believes that there is no longer any uncertainty concerning the validity of the Common Stock Increase Amendment. On December 6, 2024, Sangamo dismissed the Section 205 Application.
Item 8.01 Other Events.
On December 9, 2024, Pfizer, Inc., or Pfizer, presented detailed data from the Phase 3 AFFINE trial of giroctocogene fitelparvovec, an investigational gene therapy that Sangamo has co-developed with and licensed to Pfizer for the treatment of adults with moderately severe to severe hemophilia A, in an oral presentation at the 66th American Society of Hematology Annual Meeting and Exposition. A copy of slides from the presentation setting forth the data is filed herewith as Exhibit 99.1 and incorporated by reference herein.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
| Exhibit No. | Description | |||||||||||||
| 99.1 | ||||||||||||||
| 104 | Cover Page Interactive Data File (embedded within the 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.
| SANGAMO THERAPEUTICS, INC. | ||||||||||||||||||||
| Dated: December 9, 2024 | By: | /s/ SCOTT B. WILLOUGHBY | ||||||||||||||||||
| Name: | Scott B. Willoughby | |||||||||||||||||||
| Title: | Senior Vice President, General Counsel and Corporate Secretary | |||||||||||||||||||
1 1053 Efficacy and Safety of Giroctocogene Fitelparvovec in Adults With Moderately Severe to Severe Hemophilia A: Primary Analysis Results From the Phase 3 AFFINE Gene Therapy Trial Andrew D Leavitt1, Kaan Kavakli2, Laurent Frenzel3, Ali Bülent Antmen4, Margareth Ozelo5, Davide Matino6,7, Hazza Alzahrani8, Barbara A Konkle9, Steven W Pipe10, Jerome M Teitel11, Li-Jung Tseng12, Annie F Fang12, Florence Ganne13, Gregory DiRusso14, Jeremy Rupon14, Pascal Klaus15, Jasmine Healy16, Delphine Agathon13, Francesca Biondo17, Frank Plonski14, on behalf of the AFFINE Investigators 1University of California San Francisco, San Francisco, CA, USA; 2Ege University Faculty of Medicine, Izmir, Turkey; 3Hemophilia Care and Research, Necker Hospital, Institut Imagine, Paris, France; 4Acibadem Adana Hospital, Adana, Turkey; 5Hemocentro UNICAMP, School of Medical Sciences, University of Campinas, Campinas, Brazil; 6Thrombosis and Atherosclerosis Research Institute (TaARI), McMaster University, Hamilton, ON, Canada; 7McMaster University, Hamilton, ON, Canada; 8King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; 9Washington Center for Bleeding Disorders and the University of Washington, Seattle, WA, USA; 10University of Michigan, Ann Arbor, MI, USA; 11St. Michael's Hospital, University of Toronto, Toronto, ON, Canada; 12Pfizer Inc, New York, NY, USA; 13Pfizer Inc, Paris, France; 14Pfizer Inc, Collegeville, PA, USA; 15Pfizer Pharma GmbH, Berlin, Germany; 16Pfizer Canada ULC, Kirkland, QC, Canada; 17Pfizer Srl, Rome, Italy 66th Annual Meeting and Exposition of the American Society of Hematology (ASH), December 7–10, 2024, San Diego, CA, USA
22 • Liver-tropic recombinant AAV serotype 6 (rAAV6) vector carrying B-domain–deleted human F8 transgene enabling endogenous FVIII expression in individuals with severe to moderately severe hemophilia A • The completed Alta phase 1/2 dose-ranging study1,2 (up to 5 years) demonstrated a single infusion of giroctocogene fitelparvovec in the 3e13 vg/kg cohort (n=5) was well tolerated and resulted in: – Sustained FVIII activity levels in the moderate-to-normal range in most participants, no bleeds in the first year post infusion in all participants, and low bleeding rates through follow-up in 4 of 5 participants Giroctocogene fitelparvovec for hemophilia A AAV=adeno-associated virus; BDD=B-domain–deleted; FVIII=factor VIII; hF8=human factor 8; vg=vector genome 1. Harrington TJ, et al. Blood 2023;142(suppl 1):1054. 2. Leavitt AD, et al. Blood 2024;143(9):796–806. AAV6 Capsid Secreted FVIII protein F8 gene (in episomal form) hF8-BDD Transgene Transduction into hepatocytes Infusion of giroctocogene fitelparvovec
33 AFFINE study design AAV-6=adeno-associated virus serotype 6; ABR=annualized bleeding rate; AIR=annualized infusion rate; FVIII=factor VIII; NAb=neutralizing antibody; vg=vector genome Primary endpoint • ABR for total bleeds (treated and untreated) from Week 12 through ≥15 months Key secondary endpoints • Percentage of participants with FVIII activity level >5% at Month 15 • ABR for treated bleeds from Week 12 through ≥15 months Secondary endpoint • AIR of exogenous FVIII from Week 12 through ≥15 months Key eligibility criteria • Adult males with moderately severe to severe hemophilia A (FVIII activity level ≤1%) • No anti-AAV6 NAbs or prior history FVIII inhibitors • No significant liver dysfunction or fibrosis • No active Hepatitis B or C, well controlled HIV • No history of thrombotic events or major thromboembolic risk Screening and baselineLead-in Study 6 weeks Prospective data collection for approx. 6 months Giroctocogene fitelparvovec administration (single infusion, 3e13 vg/kg) Post-infusion period Year 2Year 1 Pre-infusion period PA PA: Primary analysis (cutoff date: 17 June 2024) • Efficacy Population (n=50) • ≥6 months follow-up in the lead-in and ≥15 months follow-up post infusion Year 3 – Year 5 5-year follow-up period
44 Participant disposition a anti-AAV-6 NAb titer ≥1:4. AAV-6=adeno-associated virus serotype 6; NAb=neutralizing antibody AFFINE SCREENING PHASE N=82 enrolled N=77 selected for treatment AFFINE PHASE 3 STUDY N=75 dosed N=75 ongoing in the follow-up phase AFFINE Efficacy Population n=50 LEAD-IN STUDY N=241 screened N=101 enrolled 115 (47.7%) participants were not eligible due to AAV6 NAb-positivitya Dosed participants who had completed ≥6 months of follow-up in the lead-in study and ≥15 months of follow-up post infusion or discontinued from the study prior to the data cutoff Discontinued from screening phase (n=5) • Not meeting eligibility criteria (n=2) • Withdrawal by participant (n=2) • Other reasons (n=1) Discontinued from treatment phase (n=2) • Lost to follow-up (n=1) • Withdrawal by participant (n=1)
Baseline demographics and characteristics a n (%) unless otherwise noted. BMI=body mass index 5 n (%)a N=75 Region North America 12 (16.0) Europe 19 (25.3) Middle East 30 (40.0) Asia Pacific 10 (13.3) South America 3 (4.0) Australia 1 (1.3) Ongoing controlled HIV 6 (8.0) History of hepatitis B 11 (14.7) History of hepatitis C 19 (25.3) Target joints at baseline 25 (33.3) n (%)a N=75 Age (range), y 32.3 (19–59) BMI ± SD, kg/m2 26.1 ± 5.1 Male 75 (100) Race White 56 (74.7) Asian 14 (18.7) Black 5 (6.7) Ethnicity Non-Hispanic 59 (78.7) Hispanic 3 (4.0) Not reported 13 (17.3)
66 Annualized bleeding rate: Total (treated and untreated) bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects. ABRtotal=annualized bleeding rate for total (treated and untreated) bleeds; CI=confidence interval; FVIII=factor VIII 0 2 4 6 8 1.24 4.73 4.65 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtotal (n=50) ABRtotal (n=49) -3.49 (-6.06, -0.91) P=0.004 -4.40 (-6.31, -2.48) P<0.0001 Superiority demonstrated vs FVIII prophylaxis (Efficacy Population, n=50) 64.0% (32/50) of participants had no bleeding events (median duration of follow-up, 33.6 months [range 14.5─44.4])
7 0 2 4 6 8 1.24 4.73 4.65 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtotal (n=50) ABRtotal (n=49) -3.49 (-6.06, -0.91) P=0.004 -4.40 (-6.31, -2.48) P<0.0001 0.26 7 Annualized bleeding rate: Total (treated and untreated) bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects. ABRtotal=annualized bleeding rate for total (treated and untreated) bleeds; CA=chromogenic assay; CI=confidence interval; FVIII=factor VIII; max=maximum; min=minimum • 1 participant had inconsistencies in bleed reporting – High number of bleeds (126, total ABR = 47.4) starting at Month 18 post infusion – Maintained FVIII activity levels >150% (via CA) through data cutoff • Median (min, max) bleeds excluding participant: 0.0 (0, 5)
0 2 4 6 8 1.24 4.73 4.65 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtotal (n=50) ABRtotal (n=49) -3.49 (-6.06, -0.91) P=0.004 -4.40 (-6.31, -2.48) P<0.0001 0.26 8 Annualized bleeding rate: Total (treated and untreated) bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects. ABRtotal=annualized bleeding rate for total (treated and untreated) bleeds; CI=confidence interval; FVIII=factor VIII Post hoc sensitivity analysis excluding 1 participant (n=49) demonstrated superiority vs FVIII prophylaxis
99 Annualized bleeding rate: Treated bleeds Numbers above graph represent treatment difference and 95% CI. Estimates and 1-sided P-value were obtained from a repeated measures generalized linear model with negative binomial distribution and identity link function with participant as a random effect and treatment and duration of follow-up (in years) as fixed effects. ABRtreated=annualized bleeding rate for treated bleeds; CI=confidence interval; FVIII=factor VIII Superiority demonstrated vs FVIII prophylaxis (Efficacy Population, n=50) 88.0% (44/50) of participants had no treated bleeds (median duration of follow-up, 33.6 months [range 14.5─44.4]) 0 2 4 6 8 4.08 M ea n AB R e st im at e (u pp er b ou nd o f 9 5% C I) Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) ABRtreated (n=50) -4.01 (-5.57, -2.45) P<0.0001 0.07
Annualized infusion rate of exogenous FVIII The mean difference (95% CI) and 1-sided P-value were obtained from paired t-test. AIR=annualized infusion rate; FVIII=factor VIII; SD=standard deviation 10 Pre infusion (FVIII prophylaxis) Post infusion (Week 12 through ≥15 months) 0 50 100 150 200 124.39 M ea n AI R (+ SD ) -124.18 (-139.47, -108.89) P<0.0001 0.21 Superiority demonstrated vs FVIII prophylaxis (Efficacy Population, n=50) 1 of 75 dosed participants resumed FVIII prophylaxis (time to resumption, 16.07 months)
FVIII activity levels post infusion CA=chromogenic assay; FVIII=factor VIII; LLOQ=lower limit of quantification 11 At Month 15, 84% (95% CI 70.9, 92.8) of participants in the Efficacy Population (n=50) had FVIII activity levels >5% (via CA); 1-sided P=0.0086 vs null hypothesis of ≤68% Week 12 Month 6 Month 12 Month 15 Month 18 Year 2 0 20 40 60 80 100 Chromogenic assay Pr op or tio n of p ar tic ip an ts Participants 75 74 55 49 30 29 FVIII Activity Level: 15–<40% >400% >230–400% >150–230% 40–150% >5–<15% 1–5% 0–<1% 56% 53% 40% 43% 40% 35% Time post infusion
12 FVIII activity levels through Year 3 Values >300% not shown. CA=chromogenic assay; BLOQ=below lower limit of quantification; FVIII=factor VIII; IQR=interquartile range; max=maximum; min=minimum; Q=quartile Fa ct or V III A ct iv ity (c hr om og en ic , % ) Post infusion (Weeks) 50% 5% Year 2 51.9 (54.43) 36.5 (BLOQ–209.2) Year 3 40.7 (39.20) 38.0 (BLOQ–105.1) 12 Week 12 mean (SD):139.7 (143.81) median (range): 88.9 (8.8–843.1) Year 1 53.3 (53.89) 38.6 (BLOQ–234.7) Box length=Q1–Q3 (IQR) Whiskers=Q1/Q3-/+1.5*IQR =mean =median =outliers
13 • No infusion interruptions or rate slowing • Infusion-related reactions (events occurring within 2 days post infusion) in 58 (77.3%) participants – Mostly mild (n=39/58; 67.2%) with resolution within 2 days • At data cutoff (mean [range] follow-up, 21.88 [7.8-44.4] months): – No FVIII inhibitors – No malignancies related to study drug – One thrombotic event in a participant with major protocol deviation (prior history of DVT and PE) and multiple thrombotic risk factors AE=adverse event; AESI=adverse event of special interest; DVT=deep vein thrombosis; FVIII=factor VIII; PE=pulmonary embolism; SAE=serious adverse event Participants with AEs, n (%) and number of events (when specified) Dosed Population N=75 AEs 74 (98.7) Number of events 740 Discontinued due to AEs 0 (0) SAEs 15 (20.0) Number of events 26 Treatment-related AEs 68 (90.7) Selected treatment-related AESIs Hepatotoxicity (transaminase increased) 47 (62.7) Infusion-related reactions 55 (73.3) Pyrexia 38 (50.7) Headache 23 (30.7) Chills 14 (18.7) Deep vein thrombosis 1 (1.3) Safety overview
14 • ALT elevations were mild and manageable – ALT elevations resolved within a median of 28.0 days • Overall, corticosteroids were well tolerated, with corticosteroid-related AEs reported in 19 (25.3%) participants • At the time of the data cutoff, no participants in the Efficacy Population remained on corticosteroids • 5 (6.7%) participants received alternative immunosuppressive therapies following corticosteroid treatment, including MMF in 4 participants, and azathioprine in 1 participant a The highest CTCAE grade among all post baseline assessments from each participant are reported. AE=adverse event; ALT=alanine aminotransferase; CTCAE=common terminology criteria for adverse events; MMF=mycophenolate mofetil; pts=participants; SAE=serious adverse event; ULN=upper limit of normal ALT and corticosteroid use N=75 Treatment-related AEs related to hepatotoxicity (transaminase increased), n (%) 47 (62.7) SAEs related to transaminase increased, n (%) 2 (2.7) Participants with ALT increase >ULN, n (%) 46 (61.3) ALT grades (CTCAE grading)a among all dosed participants, n (%) Normal 30 (40.0) Grade 1 40 (53.3) Grade 2 4 (5.3) Grade 3 1 (1.3) Grade 4 0 (0) Pts with corticosteroid use, n (%) 47 (62.7) Time to corticosteroid initiation, median (range), days 84 (7–193) Corticosteroid courses per participant, mean (range), days 2.0 (1–5) Duration of corticosteroid use, mean (range), days 114.6 (11–296) ALT elevations and corticosteroid use
15 • DOACs were well tolerated, with no significant bleeding events while on DOAC – In total, 6 participants reported ≥1 bleed while on DOAC, none were treated • 1 participant (major PD with prior history of DVT and PE and multiple thrombotic risk factors) experienced a thromboembolic event • No other thromboembolic events were reported CA=chromogenic assay; DOAC=direct oral anticoagulant; DVT=deep vein thrombosis; FVIII=factor VIII; OSA=one-stage assay; PD=protocol deviation; PE=pulmonary embolism FVIII elevations throughout follow-up N=75 ≥1 FVIII activity level >150% (CA), n (%) 37 (49.3) Time to first FVIII activity level >150%, mean (range), days 74.7 (15–540) Days with FVIII >150%, mean (range) 143.8 (4–953) Received prophylactic DOAC, n (%) 23 (30.7) Time to DOAC initiation, mean (range), days 86.13 (28–370) Total duration of DOAC, mean (range), days 166 (7–944) FVIII activity elevations
16 • A single IV infusion of 3e13 vg/kg was generally well tolerated and exhibited an acceptable and manageable safety profile • The study met the primary endpoint with a significantly reduced mean ABRtotal vs FVIII prophylaxis: 1.24 vs 4.73 (0.26 vs 4.65 in post hoc sensitivity analysis) • Mean ABRtreated was significantly reduced vs FVIII prophylaxis (0.07 vs 4.08) • Mean AIR was also significantly reduced vs FVIII prophylaxis (0.21 vs 124.39) • Mean FVIII activity levels >50% of normal (via CA) were achieved and stable up to 2 years post infusion • At the time of primary analysis, 1 participant returned to prophylaxis at month 16 Summary: Efficacy and safety of giroctocogene fitelparvovec ABRtotal=total annualized bleeding rate; ABRtreated=treated annualized bleeding rate; AIR=annualized infusion rate; CA=chromogenic assay; FVIII=factor VIII; IV=intravenous; vg=vector genome