Summary CEI continued: Key Projects Rundown / Heat Map / SE Core Team agenda recap, NeuroD SE Core Team Meeting (November 1, 2022) topics, JP Morgan Planning, Project Torchlight / Apex / Turing / Bon / Link rundown, Late Stage Scan / Prescouter, 21130 protein-degrader landscape (C4 / Plexium / Kymera / Neomorph / Wren / Anima Biotech), Meetings CEI / heat-map CEI sharepoint links

Key Projects Rundown

• (paper-clip attachment) BRTx - MG for AD Partnering Opportunity Summary.pdf — I don’t agree with a cell therapy strategy for neurodegenerative.
• Project Torchlight (Treventis). First-in-class, small molecule tau oligomer inhibitor. IND enabling stage opportunity but with areas of key concern regarding potency (in vitro and in vivo), efficacy, and translational strategy that will be address via a remediation workplan that take 6-12 months Agree
• Project Apex (Aprinoia). Alpha-syn (early lead stage)/tau PROTACs. Active preliminary DD and partnering discussions Agree
• Project Turing. Tau aggregation inhibitor Screen and early drug discovery research collaboration utilizing Takeda compounds as starting point with the universities of Cambridge and Dundee Agree
• Project Bon (Voyager). Discuss interest in moving forward for capsids with following targets: Parkin, GBA? Agree
• Project Link (Cellivery). aMTD-Parkin construct for gene therapy (viral and non-viral). Active preliminary DD. Awaiting full readout of internal evaluation of technology to move forward in partnering discussions Agree
• Project Haven (Innomedica). Talineuren®, GM1 ganglioside delivered across the BBB using company’s proprietary nanocarrier delivery system. Currently in Ph 1b in PD patients. Based on preliminary DD read-out, we will pass on a transaction. Do not feel the product as a 1x week IV infusion would be competitive in symptomatic as well as therapeutic future PD market. That said, we will review Ph 1b study results expected to be available in September 2022 Agree on passing.

Heat Map / Competitive Landscape (recap)

• Late Stage Scan. Completed earlier in the year.
• Exercise with Prescouter consultancy
  • i. Based partly on aligned Heat Map targets
    1. AD
       • a. Tau, TREM2, CD33, APOE, AQP4, EP2
    2. PD
       • a. Alpha-syn, NLRP3, GBA, Parkin, LRRK2, TRAP1, TMEM175, cGasi
  • ii. Internal Takeda SME interviews

4. Other
   • Conferences - insights
   • Open topic?

20221030

Hi All,

See below Agenda for SE Core Team Meeting. Main topic will be related to

• Start of JP Morgan Planning. What companies would we recommend for meetings? New? We have triaged a lot of opportunities, revisits?
  • We will start planning via email and look to schedule adhoc meeting to discuss live.
• Heat Map/Competitive Landscape
  • i. Prescouter will present their late/interim report and solicit feedback on their work for AD
  • ii. We have triaged a lot of opportunities. That said, high quality on strategy programs of interest have been challenging to find. Additionally with later stage focus, less commitment to do platform deals that have been a key deal type especially for innovative small molecule approaches that directly target tau and a-syn such as molecular glues and RNA modulators. How do we enable the continued external innovation?
• Upstream, Early Stage
  • a. Closer alignment with VCs driving company formation in NeuroD? Share view of world as well as early access to companies coming out of stealth.
  • b. Leverage internal investment models such as Genesis labs for “right fit” initiatives? What proposals did NeuroD make, if any?
  • c. Small scale proof of technology partnerships with key academic institutions/thought leaders?
  • d. Explore Drug Discovery Consortium? Precedents here?
• Other?
• Downstream, Later Stage?

BR, David

NeuroD SE Core Team Meeting

November 1, 2022

Topics

1. Triage. While we are actively triaging a number of opportunities, selected opportunities for live discussion

   • Ionis. We triaged this in past and there was medium interest in looking at ITGAM (synapse loss disease, i.e., e.g., schizophrenia, TBI, AD) program. Recently, the company also communicated that it would be willing to also discuss it’s APOE (AD) program. As APOE is a core target assuming we would want to include.
   • NLRP3. Recently a core group has triaged a number of NLRP3 opportunities. Have not pursued substantive discussions with any party. Have meeting aligned on interest to meet under CDA. Raj working with company on dates.
     1. Exscientia. CNS stage program. Pass
     2. Nodthera. We passed earlier in the year, but company reached out to see if we wanted to review the data from recent readout of Phase I study. Pass
     3. Denali. Have started partnering process. Looking to schedule introductory meeting.
     4. Ventyx. Pass.
     5. BioAge. Pass.
     6. Ventus. Have spoken to before. Most likely not interested. Maybe contact
     7. Halia Therapeutics. To be contacted.
     8. AC Immune. Should we reach out? Very early discovery stage
   • Transitions Bio. Biomolecular Condensate biotech. BCs implicated in sequestration of essential proteins and linked to protein aggregation in neurodegenerative disorders. Tau as potential target? This would be an early-stage platform deal. Still working on a date for confidential meeting.
   • Wren Therapeutics. Biotech with drug discovery platform for novel small-molecule medicines that block the production of toxic fleeting protein intermediates that are central to neurodegenerative disease pathways. Discovery stage program in tau. While monitored last direct engagement with company in 2019. Recently reached out to get update on progress but no response yet. Looking at alternative contact points.
   • Fluidic Analytics. Technology to measure alpha-syn seeds from human biological fluids in a highly quantitative manner. www.fluidic.com. Per Arthur - Help enable TAK-341 program and other PD and MSA programs that we may run in the future. Exploring meeting dates.

2. JP Morgan Planning. What companies would we recommend for meetings? New? We have triaged a lot of opportunities revisits? We will start planning via email and look to schedule adhoc meeting to discuss live.

3. Key Projects Rundown

   • Project Torchlight (Treventis). First-in-class, small molecule tau oligomer inhibitor. Company originally thought IND enabling but in Takeda’s opinion there are areas of key concern regarding potency (in vitro and in vivo), efficacy, and translational strategy that will be address via a remediation workplan. Have support of BDLT to move to governance for NBTS and confirmatory DD.
   • Project Apex (Aprinoia). Alpha-syn (early lead stage)/tau PROTACs. Due to negative diligence findings and inability of company to meet equity funding conditions for the structured transaction, the deal was terminated.
   • Project Turing. Tau (indirect) aggregation inhibitor screen and early drug discovery research collaboration utilizing Takeda compounds as starting point with the universities of Cambridge and Dundee. Small project endorsed by Ceri. Moving to governance for NBTS and contract negotiations.
   • Project Bon (Voyager). Over the last weeks we had several discussions with the DAU leads, Philipp, Christian and Ceri to align on the need to pursue access for BBB penetrant capsids. We aligned our interests to move forward discussions with Bon (Voyager). For all CNS indications, the current bottleneck is the delivery and an AAV capsid that allows non-surgical delivery to deep brain regions is transformative. From our current pipeline Huntington and Parkin have been selected as the top 2 targets/programs with the highest need. In addition, the team would like to get an update on the SOD1 program, as well as any new data from their capsid evolution, including efforts for muscle targets. Lastly, we have circled up with Rare Disease and they do not have a primary interest on a specific target/program at this time but would be willing to consider an option if Neuroscience eventually worked a deal out as the lead TA.
   • Project Link (Cellivery). aMTD-Parkin construct for gene therapy (viral and non-viral). Active preliminary DD. Awaiting full readout of internal evaluation of technology scheduled for December to move forward in partnering discussions. That said, key question is if are not interested in picking up brain target capsid for systemic delivery are we interested in the cell penetrating peptide technology?

4. Late Stage Scan. Completed earlier in the year. No promising/actionable opportunities.

   • Exercise with Prescouter consultancy
     • Based partly on aligned Heat Map targets
       1. AD
          • Tau, TREM2, CD33, APOE, AQP4, EP2
       2. PD
          • Alpha-syn, NLRP3, GBA, Parkin, LRRK2, TRAP1, TMEM175, cGasi
   • External and Internal Takeda SME interviews completed
   • III. Late/interim report and solicit feedback on work for AD with NeuroD SE team
   • We have triaged a lot of opportunities. That said, high quality on strategy programs of interest have been challenging to find. Additionally with later stage focus, less commitment to do platform deals that have been a key deal type especially for innovative small molecule approaches that directly target tau and a-syn such as molecular glues and RNA modulators. How do we enable the continued external innovation?
     1. Closer alignment with VCs driving company formation in NeuroD? Share view of world as well as early access to companies coming out of stealth.
     2. Leverage internal investment models such as Genesis labs for “right fit” initiatives? What proposals did NeuroD make, if any?
     3. Small scale proof of technology partnerships with key academic institutions/thought leaders?
     4. Explore Drug Discovery Consortium? Precedents here?
     5. Impact of recent clinical success of Eisai/Biogen Aβ mAb? How will this effect competitive landscape?

5. Other

   • Conferences - SFN, others?
   • Open topics?

21130

• C4 Therapeutics - Protein degrader company. Focus on oncology. Might they be willing to consider a collaboration on a tau target?
• Plexium - Protein degrader company. Main focus is oncology but they have a collaboration with Abbvie on neuroscience targets. Is this an exclusive deal? If not, might we speak with them?
• Kymera Therapeutics - Protein degrader company. Inflammation focus. Their JAK/STAT programs might have application in neuroscience. Might they be willing to work on a tau program with us?
• Neomorph - Early stage protein degrader company. Have PROTAC and MG technology. Perhaps worth learning about their approach?
• Wren Therapeutics - Early stage company focused on protein misfolding in AD including focus on oligomers. Perhaps worth learning about their approach?
• Anima Biotech - They are focused on small molecule RNA translation inhibitors. They have a tau program that is not yet partnered.

Hi Julia, Sorry I missed your message. I am available now, and any time afternoon would work for me. My number is 949 241 5449.

map CEI

• U target strategy heat map 20211221.pptx
  • https://teams.microsoft.com/l/file/96B0FCF4-2836-4586-BBF1-78A3E3335E21?tenantId=57fdf63b-7e22-45a3-83dc-d37003163aae&fileType=pptx&objectUrl=https%3A%2F%2Fmytakeda.sharepoint.com%2Fsites%2FCEINeurodegenerationWorkingTeam%2FShared%20Documents%2FGeneral%2FNDU%20target%20strategy_heat%20map%2020211118.pptx&baseUrl=https%3A%2F%2Fmytakeda.sharepoint.com%2Fsites%2FCEINeurodegenerationWorkingTeam&serviceName=teams&threadId=19:XcKcPXZdFJgJ_l7SiRI-uXVssN6ZM65gDMuYk6A88hY1@thread.tacv2&groupId=a0fd169c-f2a4-4afa-9a44-204d204

Uncertain Spans

location	transcription	uncertainty
21130 margin token	21130	partial / mistyped date prefix; possibly intended 2022-11-30 or 21-11-30.
Bottom sharepoint link	https://teams.microsoft.com/l/file/... URL	URL is clipped at the right edge and bottom edge of photo.