20240722_184226

(Verdiperstat P2 — continued from prior page)	Subject Population Probable or possible MSA according to the Gilman et al 2008 consensus criteria 'high affinity' or 'mixed affinity' binder for TSPO Period of Evaluation 12 weeks of dosing Endpoints/Objectives Primary: Change from baseline in microglial activation in striatum in TSPO PET Secondary: MPO inhibition in plasma Exploratory: UMSARS, change from baseline	May help protect neurons through inhibition of MPO-induced pathological oxidative stress AstraZeneca progressed through Phase 2 (total of 7 studies, one in MSA indication) Phase 3 study is ongoing and read out later this year
Verdiperstat P3 NCT03952806	Asset name(s) Verdiperstat; BHV-3241; AZD3241 Mechanism Myeloperoxidase inhibitor Oral; BID Sponsor Biohaven Pharmaceuticals Study Design Phase 3 Randomized, Double-Blind, Placebo-Controlled, Parallel-Group of verdiperstat versus placebo Verdiperstat 300 mg bid or placebo Sample Size 336 (actual enrollment) Subject Population Diagnosis of probable or possible MSA according to Gilman 2008 criteria (including both MSA-P and MSA-C) Anticipated survival of at least 3 years, per investigator Able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps Period of Evaluation 48 weeks Endpoints Primary: - change from baseline compared to placebo in a modified UMSARS score at week 48 - Safety and tolerability Secondary: change from baseline compared to placebo on CGI-I, MSA-QoL, UMSARS Part I and II scores
(AskBio) AAV2-GDNF gene therapy: NCT04680065 P1	Asset name(s) AAV2-GDNF gene therapy Mechanism AAV2 gene therapy of glial derived neurotrophic factor Route of administration Bilateral image-guided infusion into putamen, single dose Sponsor Brain Neurotherapy Bio, Inc, now AskBio Study Design Randomized 2:1 to AAV2-GDNF or sham surgery Blinded (comparator surgery consists of bilateral partial burr/twist holes without dural penetration) Sample Size Up to 9 subjects Subject Population MSA with sporadic, adult-onset (>30 yo) with predominant parkinsonian symptoms Less than 4 years from clinical diagnosis of MSA with expected survival > 3 years Period of Evaluation 12 months Endpoints/Objectives Primary: TEAEs over 3 yeras Secondary: Change from baseline in UMSARS compared to placebo over 12 months Percent and absolute change in ratio of specific to non-specific binding of 123I FP-CIT to DaT from baseline and compared to placebo over 12 months Change from baseline in MSA-QoL compared to placebo over 12 months
Lu AF82422, Lundbeck	P2, AMULET study, Anti-α-syn mAb, (NCT05104476) : Interventional, randomized, DB, parallel-group, placebo-controlled study to assess the efficacy, safety and tolerability of Lu AF82422 in patients with MSA The objective of the study is to find out the effect of Lu AF82422 on disease progression in participants with MSA Estimated enrollment: 60 participants Estimated study start date: November 10, 2021 Arms: 2 ☐ Lu AF82422 Arm: Participants will receive Lu AF82422 IV infusion Q4W from baseline for a minimum 48 weeks up to a maximum 72 weeks ☐ Placebo Arm: Participants will receive Lu AF82422 matching placebo IV infusion Q4W from baseline for a minimum 48 weeks up to a maximum 72 weeks Primary endpoint: Change from baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) Part I and Part II Total Score at the End of Treatment (EOT) [Time frame: Baseline to EOT (Week 48 to 72)] Secondary endpoint: Change From Baseline in the UMSARS Part I, Modified UMSARS Part I (mUMSARS) and UMSARS Part II Scores at the EOT [ Time Frame: Baseline, EOT (Week 48 to 72) ] Change From Baseline in UMSARS TS, UMSARS Part I, mUMSARS and UMSARS Part II Scores at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Schwab and England Activities of Daily Living (SE-ADL) Score at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Patient Global Impression - Severity of Illness (PGI-S) Score at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Observer-Reported Global Impression - Severity of Illness (OGI-S) Score at W 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Composite Autonomic Symptom Score Select Change (COMPASS Select Change) Score at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in UMSARS Part IV Score at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Speech, Swallowing, Falls, and Walking, as Assessed by the UMSARS Part I Item Scores at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Frequency, Cause, and Consequence of Falls, as Assessed by the Fall Diary Periods at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Score at Week 48 [ Time Frame: Baseline, Week 48 ] Percent Change From Baseline in Brain Volume, as Measured by Volumetric MRI (vMRI) at Week 48 [ Time Frame: Baseline, Week 48 ] Percent Change From Baseline in Tissue Integrity, as Measured by Diffusion-Tensor Imaging (DTI) MRI at Week 48 [ Time Frame: Baseline, Week 48 ] Change From Baseline in Neurofilament Light Chain (NfL) Concentrations at Week 48 [ Time Frame: Baseline, Week 48 ] Lu AF82422 Plasma Concentration [ Time Frame: 0 to Week 88 ] Lu AF82422 Cerebrospinal Fluid (CSF) Concentrations [ Time Frame: Weeks 48 ] Lu AF82422 CSF/Plasma Concentration Ratio [ Time Frame: Week 48 ] Estimated primary completion date: May 27, 2023 The Phase 2 AMULET study is expected to be a biomarker supported proof-of-concept study (link) ☐ This study is designed to provide early readouts for the treatment effect on neurodegenerative processes using combined biomarkers and clinical outcome measures ☐ If results from this study are positive, then Lundbeck plans to initiate a Phase 3 study with Bayesian Response-adaptive treatment allocation ☐ Goal of Bayesian Response-adaptive treatment allocation is to increase number of patients assigned to more efficacious treatment arms Lu AF82422 was granted Orphan drug designation for MSA by the EMA in April 2021 (link) (Phase 2 → Phase 3 adaptive design timeline diagram, see format_notes for full label list.) [Results]<br> 20211124: The biomarker supported Phase 2 AMULET study in MSA patients initiated in November 2021<br> 20240201:<br> Lundbeck disclosed topline results of the Ph2 AMULET study for Lu AF82422 in MSA however detailed results were not released:<br> Primary endpoint (UMSARS Part I and II Total Score) did not meet statistical significance after 48 to 72 weeks of treatment.<br> Lundbeck emphasized a positive trend with Lu AF82422 treatment in slowing disease progression, with additional signals of efficacy across additional clinical and biomarker endpoints with innovative ways of approaching the readout, which they plan to discuss with regulators.<br> All study participants were eligible to roll-over to an ongoing OLE allowing Lundbeck to collect longer term data and enabling a "delayed start" analysis.<br> Lu AF82422 was generally well tolerated, no SAEs/TAEs were shared.<br> The company highlighted that the trial was designed to demonstrate Proof of Concept and the result were encouraging, justifying a more dedicated program towards registration. Trial size and duration to be determined following a complete analysis of the Ph 2 results.<br> Although Nfl was measured in this study, they did not collect this data in the observational TALISMAN study, &amp; therefore there is limited ability to establish its clinical meaningfulness at this time.<br> What's changed?<br> In November 2023, Lundbeck disclosed plans to initiate Ph3 in 2025, no additional information was shared regarding timelines during the January 31st investor call. We will continue to closely monitor the development plan following release of full Ph2 results and regulatory meetings<br> Questions/Answer Session:<br> What is the potential next development phase (i.e., another Ph2, Ph3, or accelerated approval): Lundbeck will seek input from regulators, and if in agreement, the next development step will be with the aim of registration of the product. Lundbeck did not rule out seeking a path to accelerated approval with regulators due to the high medical need.<br> Regarding the adequacy of the trial duration on treatment effect: Lundbeck suggested a 25% slowing of disease progression in 48 weeks (primary readout) across a larger sample would be sufficient to observe clinically and statistically meaningful differences. An OLE could be leveraged to demonstrate long term safety and efficacy.<br> "time wise, I think we did a really good study in terms of the primary readout (completion of 48 weeks on drug) and maybe allow people to go on a longer time." </td> <td> received Orphan drug designation in Japan; </td> </tr> <tr> <td>...819<br>(...cinate),<br>...tent inhibitor<br>...AF1</td> <td> , a key regulatory protein in cell death pathways, apoptosis, and necrosis, and leads to neuronal cell protection in pre-clinical studies. A higher level of FAF1 is found in PD patients and could contribute to the early cell death.<br> First patient dosed in Ph2 MSA study for KM-819 (20230418),<br> Korean Ph2 study of Kainos, ... </td> <td></td> </tr>

Uncertain Spans

• The right notes column for the Verdiperstat P2 row is rendered with line wraps that clip multiple words at the right edge (e.g. inhibition of [MPO]-induced pathological oxidative stress); the bracketed words have been reconstructed from the visible word fragments and the body context.
• The Lu AF82422 right-column note received Orphan drug designation in Japan; is partially clipped at the right edge of the page; only received, designati..., and Japan; are unambiguously visible.
• The KM-819 row asset cell at the bottom of the page has a clipped left edge; the visible fragments are ...819, (...cinate),, ...tent inhibitor, ...AF1. The full asset name and citation tokens continue onto 20240722_184240.
• “Primary: TEAEs over 3 yeras” — the source typesets yeras (not years); preserved verbatim as written.