REG-Arix Bioscience PLC Imara reports Phase 2a clinical trial results of IMR-687 in adult patients with sickle cell disease  

Arix BioscienceAnnouncement

06/01/2021 14:00

============

   Arix Bioscience PLC (ARIX)
   Imara reports Phase 2a clinical trial results of IMR-687 in adult patients
   with sickle cell disease  

   06-Jan-2021 / 14:00 GMT/BST
   Dissemination of a Regulatory Announcement, transmitted by EQS Group.
   The issuer is solely responsible for the content of this announcement.

   ══════════════════════════════════════════════════════════════════════════

                              Arix Bioscience plc

                                        

   Imara reports Phase 2a clinical trial results of IMR-687 in adult patients
                            with sickle cell disease

                                        

   LONDON, 06 January 2021: Arix Bioscience plc ("Arix", LSE: ARIX), a global
   venture capital company focused on investing in and building  breakthrough
   biotech companies, notes that its  portfolio company, Imara Inc.  (Nasdaq:
   IMRA), today reported results from its Phase 2a clinical trial of  IMR-687
   in adult patients with sickle cell disease.

   Overall, the  data from  the  Phase 2a  clinical trial  demonstrated  that
   IMR-687 was  well  tolerated as  a  monotherapy and  in  combination  with
   hydroxyurea at all dose levels. In the second half of 2021, Imara  expects
   to report interim  Phase 2b data  from ongoing clinical  trials in  sickle
   cell disease and beta-thalassemia.

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

    

                                      ENDS 

                                        

   Enquiries

   For more information on Arix, please contact:

    

   Arix Bioscience plc

   Charlotte Parry, Head of Investor Relations

   +44 (0)20 7290 1072

    2 charlotte@arixbioscience.com

    

   Optimum Strategic Communications

   Supriya Mathur, Shabnam Bashir, Manel Mateus

   +44 (0)20 3922 1906

    3 optimum.arix@optimumcomms.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.

   For more information please visit:  4 www.arixbioscience.com

                                        

                                        

   Imara Reports Phase 2a Clinical Trial Results of IMR-687 in Adult Patients
                            with Sickle Cell Disease

   Promising reductions in rate of VOCs/SCPCs observed in monotherapy IMR-687
                          treated patients vs. placebo

    Biomarker data from both monotherapy IMR-687 and combination IMR-687+HU
   groups show improvement in markers of hemolysis with variable HbF results

    Reductions in hsCRP and NTproBNP in monotherapy IMR-687 treated patients
     suggest potential for lowering inflammation and cardiac stress in SCD

      IMR-687 was well tolerated as a monotherapy and in combination with
                                  hydroxyurea

      Additional data from Phase 2a open label extension trial and interim
    results from Ardent and Forte Phase 2b clinical trials expected in 2021

   BOSTON, Jan. 06, 2021 -- Imara Inc. (Nasdaq: IMRA), a clinical-stage
   biopharmaceutical company dedicated to developing and commercializing
   novel therapeutics to treat patients suffering from rare inherited genetic
   disorders of hemoglobin (Hb), today reported results from its Phase 2a
   clinical trial of IMR-687 in adult patients with sickle cell disease
   (SCD).

   "I am encouraged by the incremental data from this readout, especially in
   light of the COVID-19 pandemic challenges," said Biree Andemariam, M.D.,
   Associate Professor at UConn School of Medicine, Director of the New
   England Sickle Cell Institute at UConn Health and lead investigator for
   the Phase 2a trial. "This includes a favorable safety profile of IMR-687,
   lower rate of VOCs/SCPCs and VOC-related hospitalizations in the
   Population A1 monotherapy arm and improvements in several biomarker
   results across both the monotherapy and combination groups. I am also
   pleased by the reductions in hsCRP and NT-proBNP in the Population A1
   monotherapy arm. Both are clinically utilized biomarkers of inflammation
   and cardiac stress, respectively, and suggest that higher doses of IMR-687
   may have novel anti-inflammatory and cardiovascular benefits in sickle
   cell disease."

   "I would like to thank the patients, sickle cell disease community, and
   healthcare providers for their participation in this trial, particularly
   because the COVID-19 pandemic reduced access to clinical centers," said
   Rahul Ballal, Ph.D., President and Chief Executive Officer of Imara.
   "These incremental Phase 2a results start an important year of data
   readouts at Imara. In the first quarter of 2021, we plan to report updates
   from our Phase 2a open label extension trial, including results on 10-15
   patients. In the second half of 2021, we expect to report interim data
   from our ongoing higher dose Ardent and Forte Phase 2b clinical trials in
   sickle cell disease and beta-thalassemia, respectively."

   The Phase 2a clinical trial included a total of 93 treated patients across
   four different sub-studies and was designed to evaluate the safety,
   tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical
   outcomes of escalating doses of IMR-687 administered once daily for 16 to
   24 weeks, either as a monotherapy or in combination with hydroxyurea (HU).
   Overall, the data from the Phase 2a clinical trial demonstrated that
   IMR-687 was well tolerated as a monotherapy and in combination with HU at
   all dose levels. There were no observed clinically significant shifts in
   vital signs or electrocardiogram data, including no hypotension or
   neutropenia in either the monotherapy or combination arms. Interim data on
   patients from Populations A and B were previously disclosed, with results
   from the A1 and B1 populations being reported for the first time.

   Monotherapy Sub-studies (A/A1):
   Population A (n=40): Patients received either placebo or IMR-687 at
   once-daily doses of 50 mg or 100 mg through 12 weeks and then higher doses
   of 100 mg or 200 mg, respectively, through an additional 12 weeks (24
   weeks total).

   Population A1 (n=18): Patients received either placebo or IMR-687 at a
   once-daily dose of 100 mg through 4 weeks and then 200 mg through an
   additional 20 weeks (24 weeks total).

   Combination Sub-studies (B/B1):
   Population B (n=21): Patients received either placebo or IMR-687
   once-daily at 50 mg on top of a stable dose of standard of care HU, with
   escalation after 4 weeks to 100 mg for an additional 12 weeks (16 weeks
   total).

   Population B1 (n=14): Patients received either placebo or IMR-687
   once-daily at 50 mg on top of a stable dose of standard of care HU, with
   escalation after 4 weeks to 100 mg for an additional 20 weeks (24 weeks
   total).

   Population A1 (monotherapy)
   The most frequent adverse events in the IMR-687 treatment arm included
   sickle cell anemia with crisis, nausea, headache and back pain and were
   generally consistent with those observed at two previously reported
   interim analyses. A 25% lower rate of vaso-occlusive crises/sickle
   cell-related pain crises (VOCs/SCPCs), as part of the safety analysis, was
   observed in the IMR-687 treatment group when compared to placebo. 58% of
   patients (7 of 12, 9 events total) experienced at least one VOC/SCPC in
   the IMR-687 treatment group as compared to 83% (5 of 6, 14 events total)
   in the placebo population. Furthermore, the rate of VOC-related
   hospitalizations was lower in the IMR-687 treatment group when compared to
   placebo. 33% of patients (4 of 12) experienced one VOC-related
   hospitalization in the IMR-687 treatment group as compared to 66% (4 of 6)
   in the placebo population.

   Biomarker results showed no meaningful changes in F-cells, fetal
   hemoglobin (HbF) levels, or Hb levels from baseline through week 24.
   However, a dose-dependent increase in HbF (1.3% absolute increase) was
   seen when patients dose escalated from 100 mg to 200 mg, starting after 4
   weeks and through 24 weeks. One of seven evaluable patients (14%) in
   Population A1 recorded an absolute increase in HbF percentage from
   baseline of greater than 1% (increase of 3.2%). Markers of hemolysis that
   include percent reticulocytes, absolute reticulocyte count, indirect
   bilirubin and LDH all improved from baseline in a dose dependent manner,
   with the greatest improvement occurring when patients were on the 200 mg
   dose. This trend similarly occurred with high sensitivity C-reactive
   protein (hsCRP) and amino-terminal pro-brain type natriuretic peptide
   (NT-proBNP) values. Placebo patients from Population A1 did not have
   evaluable week 24 PD biomarker results due in part to missing study visits
   and are therefore not included in the table below. A summary of the mean
   results from the IMR-687 treatment arm are as follows:

   Measure                              Baseline Week 24 Percent Change from
                                        Value    Value   Baseline to Week 24
   HbF percentage (%)                   8.8      8.7     -1.1%
   F-cell percentage (%)                28.1     28.5    1.4%
   Hb (g/dL)                            8.8      8.6     -2.3%
   Markers of Hemolysis
   Percent reticulocytes (%)            10.4     7.4     -28.8%
   Absolute reticulocyte count (×109/L) 296      240     -18.9%
   Indirect bilirubin (µmol/L)          61.4     44.0    -28.3%
   LDH (IU/L)                           397      346     -12.8%
   Markers of Inflammation & Cardiac Stress
   hsCRP (mg/L)                         10.4     2.5     -75.9%
   NTproBNP (ng/L)                      685      414     -39.6%

   Population B1 (combination therapy)
   The most frequent adverse events in the IMR-687+HU treatment arm included
   headache, sickle cell anemia with crisis and nausea and were generally
   consistent with those observed in Population A1. There were no meaningful
   differences in VOCs/SCPCs or VOC related hospitalizations, between the
   IMR-687+HU and HU+placebo groups.

   Biomarker results in IMR-687+HU treated patients showed an overall
   increase in F-cells and HbF levels from baseline to week 24, while Hb
   levels did not meaningfully change. Three of the eight evaluable subjects
   (33%) had absolute increases in HbF percentage of greater than 1%, with a
   mean absolute increase in HbF percentage of 4.3% in that subset of
   patients. Dose dependent improvements in several markers of hemolysis were
   observed from baseline through week 24, with the greatest improvement
   occurring when patients were on the 100 mg dose. hsCRP and NT-proBNP
   values through week 24 slightly increased from baseline. There was a
   single placebo patient from Population B1, as other patients did not have
   evaluable week 24 PD biomarker data due in part to missing study visits.
   Therefore, this single patient is not included in the table below. A
   summary of the mean results from the IMR-687+HU treatment arm are as
   follows:

   Measure                              Baseline Week 24 Percent Change from
                                        Value    Value   Baseline to Week 24
   HbF percentage (%)                   18.6     19.8    6.5%
   F-cell percentage (%)                58.8     61.4    4.4%
   Hb (g/dL)                            9.5      9.4     -1.1%
   Markers of Hemolysis
   Reticulocytes (%)                    7.5      5.3     -29.3%
   Absolute reticulocyte count (×109/L) 185      137     -25.9%
   Indirect bilirubin (µmol/L)          34.9     37.9    8.6%
   LDH (IU/L)                           351      340     -3.1%
   Markers of Inflammation & Cardiac Stress
   hsCRP (mg/L)                         11.5     12.5    8.7%
   NTproBNP (ng/L)                      284      317     11.6%

   Population A/B (monotherapy, combination therapy)
   Imara previously reported interim results within Populations A and B.
   Subsequently, four additional patients completed 24 weeks of dosing in the
   Population A monotherapy arm. A completers analysis in this group showed
   that the high dose of IMR-687 (100 mg/200 mg) resulted in a relative
   increase in F-cell percentage of 13.3% from baseline (p=0.025) and a mean
   absolute increase in HbF percentage from baseline of 0.9%. Three of the
   eight evaluable subjects (38%) in Population A recorded absolute HbF
   percentage increases of greater than 1%, with a mean absolute increase in
   HbF percentage of 3.1% in that subset of patients.  

   In Population B, we examined the PK of IMR-687+HU as compared to HU alone.
   The PK data in the second interim analysis indicated that treatment with
   IMR-687+HU did not result in changes in HU PK.

   Imara anticipates that it will present additional study details at a
   future medical meeting.

   About IMR-687

   IMR-687 is a highly selective and potent small molecule inhibitor of PDE9.
   PDE9 uniquely degrades cyclic guanosine monophosphate (cGMP), an active
   signaling molecule that plays a role in vascular biology. Lower levels of
   cGMP are often found in people with sickle cell disease and
   beta-thalassemia and are associated with impaired blood flow, increased
   inflammation, greater cell adhesion and reduced nitric oxide-mediated
   vasodilation.

   Blocking PDE9 acts to increase cGMP levels, which are associated with
   reactivation of fetal hemoglobin, or HbF, a natural hemoglobin produced
   during fetal development. Increased levels of HbF in red blood cells have
   been demonstrated to improve symptomology and lower disease burden in
   patients with sickle cell disease and patients with beta-thalassemia.

   About Imara

   Imara Inc. is a clinical-stage biotechnology company dedicated to
   developing and commercializing novel therapeutics to treat patients
   suffering from rare inherited genetic disorders of hemoglobin. Imara is
   currently advancing IMR-687, a highly selective, potent small molecule
   inhibitor of PDE9 that is an oral, once-a-day, potentially
   disease-modifying treatment for sickle cell disease and beta-thalassemia.
   IMR-687 is being designed to have a multimodal mechanism of action that
   acts on red blood cells, white blood cells, adhesion mediators and other
   cell types. For more information, please visit  5 www.imaratx.com.

   Cautionary Note Regarding Forward-Looking Statements

   Statements in this press release about future expectations, plans and
   prospects, as well as any other statements regarding matters that are not
   historical facts, may constitute "forward-looking statements" within the
   meaning of The Private Securities Litigation Reform Act of 1995. These
   statements include, but are not limited to, statements relating to the (i)
   plan to release additional data on the Phase 2a clinical trial of IMR-687
   in patients with sickle cell disease, (ii) content of, and timing with
   respect to, the reporting of data from the open label extension clinical
   trial evaluating IMR-687 in patients with sickle cell disease, (iii)
   clinical trial design and timing with respect to reporting of data from
   the Ardent and Forte Phase 2b clinical trials in patients with sickle cell
   disease and beta-thalassemia and (iv) the Company's beliefs regarding the
   strength of its clinical data, the tolerability and therapeutic potential
   of IMR-687 and advancement of its clinical program. The words
   "anticipate," "believe," "continue," "could," "estimate," "expect,"
   "intend," "may," "plan," "potential," "predict," "project," "should,"
   "target," "will," "would" and similar expressions are intended to identify
   forward-looking statements, although not all forward-looking statements
   contain these identifying words. Actual results may differ materially from
   those indicated by such forward-looking statements as a result of various
   important factors, including the impact of extraordinary external events,
   such as the risks and uncertainties resulting from the impact of the
   COVID-19 pandemic on the Company's business, operations, strategy, goals
   and anticipated milestones, including its ongoing and planned research
   activities and ability to conduct and readout data from its ongoing
   clinical trials of IMR-687; the Company's ability to advance the
   development of IMR-687 under the timelines it projects in current and
   future clinical trials, demonstrate in any current and future clinical
   trials the requisite safety and efficacy of IMR-687, replicate scientific
   and non-clinical data in both subsequent case report readouts and in
   clinical trials and other factors discussed in the "Risk Factors" section
   of the Company's most recent Quarterly Report on Form 10-Q, which is on
   file with the Securities and Exchange Commission and in other filings that
   the Company makes with the Securities and Exchange Commission in the
   future. Any forward-looking statements contained in this press release
   speak only as of the date hereof, and the Company expressly disclaims any
   obligation to update any forward-looking statement, whether as a result of
   new information, future events or otherwise.

   Media Contact:
   Gina Nugent
   Ten Bridge Communications
   617-460-3579
    6 gina@tenbridgecommunications.com

   Investor Contact:
   Michael Gray
   617-835-4061
    7 mgray@imaratx.com

                                        

   ══════════════════════════════════════════════════════════════════════════

   ISIN:           GB00BD045071
   Category Code:  MSCU
   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.:   90965
   EQS News ID:    1158842


    
   End of Announcement EQS News Service

   ══════════════════════════════════════════════════════════════════════════

    8 fncls.ssp?fn=show_t_gif&application_id=1158842&application_name=news&site_id=reuters8

References

   Visible links
   1. https://eqs-cockpit.com/cgi-bin/fncls.ssp?fn=redirect&url=c25cae91115e29ce24fe17b31c24cb49&application_id=1158842&site_id=reuters8&application_name=news
   2. mailto:charlotte@arixbioscience.com
   3. mailto:optimum.arix@optimumcomms.com
   4. https://eqs-cockpit.com/cgi-bin/fncls.ssp?fn=redirect&url=889c637ce21c3a47a35c39202ebd9825&application_id=1158842&site_id=reuters8&application_name=news
   5. https://eqs-cockpit.com/cgi-bin/fncls.ssp?fn=redirect&url=7047a4bf9dff3ee66ea15a78dfc8284f&application_id=1158842&site_id=reuters8&application_name=news
   6. mailto:gina@tenbridgecommunications.com
   7. mailto:mgray@imaratx.com


============