1. NXT007 Presentations
1.1. NXT007 Program Update to LCT November 2022
1.2. NXT007 Update to the LCT - 23.9.2023
1.3. Presentation 20.11.23
1.3.1. Messaging - April 2023 - Olivia
1.4. NXT007 Market Opportunity Space and Differentiation - Final outputs & recommendations - 30.11.22
1.5. NXT007 - Roche/Chugai Joint Steering Committee (JSC) - 12 November 2024
2. NXT007 Commercialization Team
2.1. Agenda and Notes
2.1.1. 90 days priorities
3. F8 Equivalence -> Tovo on 24.8.22
3.1. There is some data using TGA (Thrombin Generation Assay) and it suggests an activity ~40% for NXT007.
3.2. Preclinically we will run additional evaluations using an organ-on-a-chip and in vivo models.
3.3. No matter what, the clinical data will supersede any preclinical observations.
3.4. FVIII equivalence Narrative_April 2022_update
3.4.1. Slide 37
4. Chugai
4.1. Chugai Team (Update from June 2023)
4.1.1. Project Leader: Tatsuya Robin Koyama Pre-clinical leader(pharmacology): Atsushi Muto Robin has been in NXT007 team in 4 years as Clinical leader. We believe that he will lead NXT007 project based on his clinical experiences. Rota will lead both Hemlibra and NXT007 clinical team. He will advance both Hemlibra and NXT007 clinical team based on his scientific ability and management skills. Muto-san has been involved with ACE910 since its research stage, and he will lead deep-dive discussion in preclinical data of NXT007. Chugai hemophilia area leader, Suguru Kenmoku and Chugai Hemlibra LCL, Meiri Kawazoe will support in very close collaboration with Robin and NXT007 team to be more attractive team.
5. INN for NXT007
5.1. Aug 23 WS Pre-Read
5.1.1. List of INN names
6. ClinicalTrials.gov
6.1. NXT007 multiple-ascending-dose study ph1/2 is now (15.8.23) on clinical trials.gov and therefore public.
7. PHC
7.1. Nicky Slides Sept 2023
7.1.1. Dan H response to slides
8. NXT007 - What is it?
8.1. Preclicical insights
8.1.1. Competitor therapies
8.1.1.1. Thrombine generation
8.1.1.1.1. Efficacy and safety
8.2. In vivo study - study design
8.2.1. ..
8.2.1.1. ...
8.2.1.1.1. ...
9. Integrated Comms Plan (15.5.2024
9.1. NXT007 Programm Overview (Sept 2023)
10. NXT007 TPP (Olivia)
10.1. Email 23.5.
10.1.1. Slide Deck
11. NXT007 IDCP
11.1. Key Strategic Questions (KSQ) NXT007
11.2. Integrated Development and Commercialization Plan (IDCP)
12. Key Strategic Questions (KSQ) NXT007 - Sept 2024
12.1. Situational Analysis - Sept 2024
13. NXT007 Narrative
13.1. Consider start taking NXT and never see a Hematologist again Consider start taking NXT and never need a factor product any more Consider start taking NXT and never have a spontaneous bleed again Consider start taking NXT and go to the dentist whenever you want Consider start taking NXT and travel spontaneously to your favorable holiday location Consider start taking NXT and never loose a day of work because of bleeds again Consider start taking NXT and never loose a day of school because of bleeds again Consider start taking NXT and not having to tell your friends that you have Hemophilia Consider start taking NXT and have no burden or concerns on your mind any more Consider start taking NXT and be as active as you always wanted to be Consider start taking NXT and know that you created the safest and best future for your child Consider start taking NXT and feel that you have taken the best choice for yourself and your families and friends Consider start taking NXT to have a good perspective of growing old as a haemophiliac Consider start taking NXT to experience a comfortable administration experience
14. LCT BiSpecifics
14.1. Priorities - LCP Opportunities - June 2023
15. NXT007 - What is it?
15.1. N = factor Nine X = upper part of X standing for v for bridging T = factor Ten
15.1.1. 0 = zero bleeds happen 0 = zero coagulation factor needed 7 = first patient in phase I clinical trial in 1917
15.2. A next-generation humanized FAST-IgTM bispecific monoclonal antibody
15.3. NXT007 is a humanized monoclonal modified IgG4 antibody with a bispecific antibody structure that binds to FIXa and FX to mimic the function of FVIII. NXT007 has the same mode of action bridging FIXa and FX as emicizumab which is now approved for prophylaxis in more than 100 countries. NXT007 accelerates FX activation by FIXa in patients with HA who have loss of function and/or reduced FVIII activity, promoting effective downstream hemostasis. Preclinical studies show NXT007 has higher FVIII-mimetic activity than emicizumab. This higher potency is expected to achieve increases in hemostatic activity into the non-hemophilic level (i.e., FVIII activity > 40 IU/dL). Since NXT007 shares no sequence homology with FVIII, it can exert its FVIII-mimetic activity in patients with Hemophilia A irrespective of the presence of FVIII inhibitors. Additionally, as an IgG bispecific antibody therapy, NXT007 has a novel Fc modification that theoretically affords further half-life (t1/2) prolongation compared to emicizumab.
16. NXT007 Teams
16.1. NXT Teams there are: PT, extended PT, CT, preclinical, biomarker (TBD)
16.2. My Teams Dashboard
16.3. Available D-lists for NXT007 specifically:
16.3.1. Glohemophilia_NXT007_RochePT Glohemophilia_NXT007_RochePT_extended (includes Glohemophilia_NXT007_RochePT) Glohemophilia_NXT007_Roche_CT Glohemophilia_NXT007_Roche_preclinteam
16.4. Admin Info
16.4.1. @ Presenters: Please name your pre-reads and supporting documents per this structure: [YYYMMDD]_[Title] _ [presenter]_NXT007_PTmeeting_["preread", if preread only] Please upload your pre-read and/or supporting materials onto the meeting specific folder here by Friday 06 sept midday. Please insert the hyperlink to your materials into the agenda file, columns "link to slides".
17. NXT007 Study Numbers
17.1. NXT007 vs FVIII study: WO45886 NXT007 vs Emi study: BO45887 NXT007 in Pediatrics: BO45888
18. Q&As
18.1. What is NXT007
18.1.1. NXT007 is a humanized monoclonal modified IgG4 antibody with a bispecific antibody structure that binds to FIXa and FX to mimic the function of FVIII. NXT007 has the same mode of action bridging FIXa and FX as emicizumab which is now approved for prophylaxis in more than 100 countries. NXT007 accelerates FX activation by FIXa in patients with HA who have loss of function and/or reduced FVIII activity, promoting effective downstream hemostasis. Preclinical studies show NXT007 has higher FVIII-mimetic activity than emicizumab. This higher potency is expected to achieve increases in hemostatic activity into the non-hemophilic level (i.e., FVIII activity > 40 IU/dL). Since NXT007 shares no sequence homology with FVIII, it can exert its FVIII-mimetic activity in patients with HA irrespective of the presence of FVIII inhibitors. Additionally, as an IgG bispecific antibody therapy, NXT007 has a novel Fc modification that theoretically affords further half-life (t1/2) prolongation compared to emicizumab.
18.2. How and when do we start considering patient input into the the upcoming NXT007 trials?
18.2.1. for phase III?
18.2.1.1. for phase II?
18.2.2. What are the timelines of the development plan?
18.3. How can the protocol design be optimized
18.3.1. new or additional endpoints
18.3.2. trial participants and centers
18.3.3. Comparator therapy
18.4. Difference betw. Emi and 007
18.4.1. NXT007 vs Hemlibra
19. Future Therapies OUTLOOK
19.1. ....
20. Chrono - Work Plan: Status 12.11.22
20.1. Next steps that will happen until PivGo
20.1.1. 1. Development Board presentation & feedback: December 2024 2. Business Board presentation & feedback: January 2025 3. fPOC/Dose selection: February 2025 4. Merge IDCP into new 'End-to-End Asset Strategy' format 5. PivGo: expected March 2025
21. NXT007 CDP
22. NXT007 Single source of truth (SSOT) Slides (reference document)
22.1. NXT007 TPP Single Source of Truth (Dan File)
23. NXT TPP
23.1. NXT CDP
24. Novel Endpoints
24.1. Team
24.1.1. Team = Charlotte Vignal (Team Lead)
24.1.1.1. Slides - Hemophilia Study Design WG
24.2. Endpoint Goals
24.2.1. To get NXT007 approved
24.2.1.1. Need to be more effective that emi
24.2.1.1.1. Problem: bleed rates are so low already
24.2.2. EP considerations
24.2.2.1. Difference betw. clinical trail setting and what people in the real world need and experience
24.2.3. EP Considerations
24.2.3.1. What patients to involve in what countries?
24.2.3.1.1. More women
24.2.3.1.2. Infants as well
24.2.3.2. EP
24.2.3.2.1. which are relvant
24.2.4. EP
24.2.4.1. Patient Relevant when comparing with emi
24.2.4.1.1. Dental Care -> Free of Factor Use
24.2.4.1.2. Female Issues
24.2.4.1.3. Surgeries
24.2.4.1.4. Travelling
24.2.4.1.5. Painfree adminiistration -> filter needle
24.2.5. Defining Novel Endpoints in Hemophilia WG
24.2.6. PROBE
24.2.6.1. MarSkinner 23.11.22
24.2.6.1.1. We now have quite a bit of experience in clinical studies, investigator initiated studies and national patient organization projects. This seems like an excellent opportunity.
24.3. G-sites
24.3.1. End point and Outcomes
25. Phase III
25.1. Patient Types INCLUDED
25.1.1. Servere HA + MODERATE people with HA
25.1.2. More WOMEN with HA -> moderate allows for more women to be included
25.1.3. INFANTS should also be included if clinically no risk
25.1.4. vWD Type 3 ?
25.1.4.1. Michaela: we are planning a work up of this indication for Hemlibra first, based on Tovos results, which would need to show evidence beyond Type 3
26. Phase I/II - Roche
26.1. Ph1/2 (NXATGE) study
26.1.1. Target population
26.1.1.1. Healthy volunteers (Single Ascending Dose part) and hemophilia A without inhibitor >=12yrs who are treated by FVIII and hemophilia A with/without inhibitor >=12yrs who are treated by Emi in MAD parts
26.1.1.2. does NOT contain pediatrics/infants and women since the Ph1/2 study is first human study and the objectives are to evaluate safety, tolerability and efficacy by dose escalation
27. Roche Team
27.1. Project Team (PT) -> George
27.1.1. Below that -> Clinical Team (CT) -> Dan
27.2. NXT007 Combined TEAM
27.2.1. Team Charter (April 2024)
28. Juno (Veronica Rio Diaz)
28.1. Biomarkers, assay characteristics
28.1.1. slides of December 2023