REG-Arix Bioscience PLC Imara Announces Results of Interim Analyses of Tovinontrine (IMR-687) Phase 2b Clinical Trials in Sickle Cell Disease and Beta-Thalassemia

Arix BioscienceAnnouncement

05/04/2022 16:30

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   Arix Bioscience PLC (ARIX)
   Imara Announces Results of Interim Analyses of Tovinontrine (IMR-687)
   Phase 2b Clinical Trials in Sickle Cell Disease and Beta-Thalassemia

   05-Apr-2022 / 16:28 GMT/BST
   Dissemination of a Regulatory Announcement, transmitted by EQS Group.
   The issuer is solely responsible for the content of this announcement.

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   PRESS RELEASE

                                        

                              Arix Bioscience plc

    

     Imara Announces Results of Interim Analyses of Tovinontrine (IMR-687)
      Phase 2b Clinical Trials in Sickle Cell Disease and Beta-Thalassemia

    

   LONDON, 05 April 2022:  Arix Bioscience plc  ("Arix", LSE:ARIX), a  global
   venture capital company focused on investing in breakthrough biotechnology
   companies, notes that  its portfolio company,  Imara Inc. (Nasdaq:  IMRA),
   today announced  results from  interim  analyses of  its Ardent  Phase  2b
   clinical trial  of tovinontrine  (IMR-687) in  patients with  sickle  cell
   disease (SCD)  and  Forte  Phase  2b clinical  trial  of  tovinontrine  in
   patients with beta-thalassemia. Imara also  announced that because of  the
   data generated by these interim analyses, the company will discontinue the
   Ardent and Forte trials as well as the further development of tovinontrine
   in sickle cell disease and beta-thalassemia.

    

   As of close  of business on  4 April  2022 Arix held  2,344,072 shares  in
   Imara.

    

   The   announcement   can    be   accessed   on    Imara's   website    at:
    1 https://imaratx.com/ and full  text of the  announcement from Imara  is
   contained below.

    

    

                                      ENDS 

   For more information on Arix, please contact:

    

   Arix Bioscience plc

   +44 (0)20 7290 1050

    2 ir@arixbioscience.com  

    

   Powerscourt Group

   Sarah MacLeod, Ibrahim Khalil

   +44 (0)20 7250 1446

    3 arix@powerscourt-group.com

    

   About Arix Bioscience plc

   Arix Bioscience  plc  is  a  global venture  capital  company  focused  on
   investing  in   and  building   breakthrough  biotech   companies   around
   cutting-edge advances in life sciences.

   We collaborate  with exceptional  entrepreneurs and  provide the  capital,
   expertise  and  global  networks  to  help  accelerate  their  ideas  into
   important new treatments for patients. As a listed company, we are able to
   bring this exciting  growth phase of  our industry to  a broader range  of
   investors.  4 www.arixbioscience.com

                                        

                                        

                                        

                                        

                                        

                              Imara Press Release

     IMARA ANNOUNCES RESULTS OF INTERIM ANALYSES OF TOVINONTRINE (IMR-687)
      PHASE 2B CLINICAL TRIALS IN SICKLE CELL DISEASE AND BETA-THALASSEMIA

   April 5, 2022 at 6:45 AM EDT

                                        

       Interim results in Ardent trial for sickle cell disease showed no
   significant difference in median annualized rate of vaso-occlusive crises
       in high-dose group versus placebo in an intent-to-treat population

      Interim results in Forte trial for beta-thalassemia demonstrated no
        meaningful benefit in transfusion burden or improvement in most
                           disease-related biomarkers

            Tovinontrine was generally well-tolerated across studies

    Both Phase 2b clinical trials and further development of tovinontrine in
              sickle cell and beta-thalassemia to be discontinued

   BOSTON, April 05, 2022 (GLOBE NEWSWIRE) -- Imara Inc. (Nasdaq: IMRA) today
   announced results from interim analyses of its Ardent Phase 2b clinical
   trial of tovinontrine (IMR-687) in patients with sickle cell disease (SCD)
   and Forte Phase 2b clinical trial of tovinontrine in patients with
   beta-thalassemia. Imara also announced that because of the data generated
   by these interim analyses, the company will discontinue the Ardent and
   Forte trials as well as the further development of tovinontrine in sickle
   cell disease and beta-thalassemia.

   "We are disappointed in the outcome of both of the interim analyses in our
   Phase 2b studies for sickle cell disease and beta-thalassemia, and
   particularly that the Ardent trial interim analysis did not replicate our
   previously observed positive vaso-occlusive crisis data," said Rahul
   Ballal, Ph.D., President and Chief Executive Officer of Imara. "We plan to
   discontinue both studies during the second quarter. As we do this, we
   remain deeply grateful to the patients, investigators and their teams for
   their participation in these trials and to the extended Imara team for
   their role and dedication in generating the comprehensive interim
   results."

   Dr. Ballal continued, "Moving forward, we plan to consider our strategic
   options, including development of tovinontrine in heart failure with
   preserved ejection fraction (HFpEF) as well IMR-261 clinical development
   plans."

   Ardent Phase 2b Sickle Cell Disease Interim Analysis:
   The interim analysis for the Ardent trial was conducted when all
   participants completed the week 24 assessment or terminated early. The
   intent-to-treat (ITT) population was used for the primary efficacy
   analysis, which is a comparison of the median annualized vaso-occlusive
   crisis (VOC) rate between the high dose tovinontrine group (n=47, once
   daily oral dose of 300 mg or 400 mg based on patient weight) and placebo
   group (n=32).

   Safety was analyzed across all participants enrolled in the Ardent trial,
   including the high dose, low dose (n=33, 200 mg or 300 mg once daily oral
   dose based on patient weight) and placebo groups. Data from the interim
   analysis demonstrated that tovinontrine was generally well-tolerated, with
   the most frequent adverse events (>=10% of participants in any treatment
   group) considered at least possibly related to study drug by the
   investigator being nausea, headache, dizziness and vomiting. Four (3.6%)
   participants discontinued prior to week 24 due to adverse events.

   The median annualized VOC rate in the placebo group was 2.02 VOCs per year
   and was 1.89 VOCs per year in the high dose tovinontrine group, for a
   treatment difference of 0.13 VOCs per year, or 6.4%. Based on the minimal
   decrease observed in VOCs with the high dose and low VOC rate in the
   placebo arm, Imara enacted an addendum to the statistical analysis plan
   for the trial and noted trends of VOC benefit with tovinontrine. The
   median annualized rate of VOCs in the low dose tovinontrine group was
   zero, as compared to 2.02 in the placebo group, and as compared to
   placebo, the low dose tovinontrine group experienced an increase in median
   time to first VOC and a higher proportion of participants who were
   VOC-free. A trend for lower median annualized rate of VOCs was also
   observed for participants in the high and low dose tovinontrine groups on
   monotherapy (not on background hydroxyurea) as compared to placebo.
   Although these additional data are encouraging, none were statistically
   significant. In addition, no meaningful difference was observed in fetal
   hemoglobin (HbF) response in either the high or low dose tovinontrine
   groups as compared to placebo. Collectively, the overall additional data
   did not materially increase the likelihood of success for this trial.

   Forte Phase 2b Beta-thalassemia Interim Analysis:
   The Forte trial interim analysis evaluated safety and biomarker data for
   both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent
   thalassemia (NTDT) cohorts, as well as data on transfusion burden
   reduction in the TDT cohort. In both cohorts, tovinontrine was
   well-tolerated, with the most frequent adverse events (>=10% of
   participants in any treatment group) considered at least possibly related
   to study drug by the investigator being nausea and headache. One NTDT and
   eight TDT participants (3.3% and 10.8%, respectively) discontinued study
   drug due to adverse events.  

   Participants in the TDT cohort of the Forte trial were randomized to
   either placebo (n=20), low dose (n=25, 200 mg or 300 mg) or high dose
   (n=29, 300 mg or 400 mg). No meaningful benefit was observed in
   transfusion burden in either tovinontrine group when compared to placebo.
   Participants in the NTDT cohort of the Forte trial were randomized to
   either placebo (n=7), low-dose group (n=8, 200 mg or 300 mg), or high-dose
   group (n=14, 300 mg or 400 mg). No meaningful improvements were observed
   in most disease-related biomarkers, including total hemoglobin (Hb).

   About the Ardent Phase 2b Clinical Trial
   The Ardent study was a randomized, double-blind, placebo-controlled,
   multicenter Phase 2b study in adult patients with sickle cell disease
   (SCD) randomized to either placebo, low-dose tovinontrine (200 mg or 300
   mg) or high-dose tovinontrine (300 mg or 400 mg). The primary efficacy
   endpoint was annualized rate of VOCs in participants dosed with high dose
   tovinontrine as compared to placebo. The key secondary endpoints were time
   to first VOC and proportion of participants with fetal hemoglobin (HbF)
   response, defined as an absolute increase from baseline of at least 3% in
   HbF in the high dose group vs placebo.

   About the Forte Phase 2b Clinical Trial
   The Forte study was a randomized, double-blind, placebo-controlled,
   multicenter Phase 2b clinical trial evaluating the safety and tolerability
   of tovinontrine in adult patients with beta-thalassemia. Patient
   randomization was stratified by transfusion-dependent thalassemia (TDT) or
   non-transfusion-dependent thalassemia (NTDT). The primary objective of the
   study was safety and tolerability. For TDT participants, the clinical
   trial also evaluated the effect of tovinontrine versus placebo in reducing
   transfusion burden. For NTDT participants, the clinical trial also
   evaluated the effect of tovinontrine versus placebo on fetal hemoglobin as
   well as total hemoglobin.

   About Tovinontrine (IMR-687)
   Tovinontrine is a highly selective and potent small molecule inhibitor of
   phosphodiesterase-9 (PDE9). Tovinontrine has a multimodal mechanism of
   action that acts on red blood cells, white blood cells, adhesion molecules
   and blood vessels. PDE9 selectively degrades cyclic guanosine
   monophosphate (cGMP), an active signaling molecule that plays a role in
   vascular biology.

   About Imara
   Imara Inc. is a clinical-stage biotechnology company dedicated to
   developing and commercializing novel therapeutics to treat patients
   suffering from serious diseases. Imara is considering development plans
   for tovinontrine in heart failure with preserved ejection fraction
   (HFpEF), as well as for IMR-261, an oral activator of nuclear factor
   erythroid 2-related factor 2, or Nrf2. For more information, please
   visit  5 www.imaratx.com.

    

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   ISIN:           GB00BD045071
   Category Code:  PFU
   TIDM:           ARIX
   LEI Code:       213800OVT3AHQCXNIX43
   OAM Categories: 3.1. Additional regulated information required to be
                   disclosed under the laws of a Member State
   Sequence No.:   153844
   EQS News ID:    1321059


    
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