Cerevance Pipeline (CVN424 / CVN766 / CVN293 / CD38 / KCNJ6 / GPR65), Current Portfolio Status: April 2022 timeline, Key worlds (evaluation / scientific confidence / Opportunity), Team table (function ↔ team member)

Pipeline

Target	target	mechanism			Design
CVN424	GPR6 inverse agonist, small molecule, - GPR6 is an orphan GPCR that has enriched expression in the striatopallidal, indirect pathway, MSN neurons of the striatum - a target present in striatal neurons that express dopamine receptor D2. The company claims that CVN424 does not affect D1-dependent pathways, and that this selective targeting will help avoid LID associated with D1 activation. CVN424 is being developed as an add-on to L-DOpa				P2	2019, a Phase 2, randomized, place-controlled study began enrolling 66 people with Parkinson's who experience motor fluctuations on a stable dose of levodopa. To be eligible, patients must average more than 2 hours per day of "off time," i.e., periods when symptoms reappear between levodopa doses. Participants will be randomized to high or low dose drug or placebo, taken as an oral suspension once daily for one month. The primary outcomes are adverse events and safety measures; secondary outcomes include an unspecified efficacy measures, and pharmacokinetics. This trial takes place at 16 sites across the U.S., and is expected to end in 2020. [Results] Beyond meeting safety objectives, the drug achieved a significant and meaningful, dose-dependent reduction of "OFF time"
					P1	2019, Cerevance completed a Phase 1 single- and multiple-dose safety study in healthy adults. Sixty-six volunteers received single CVN424 doses from 1 to 225 mg, or seven daily doses of 25, 75, and 150 mg or matching placebo. According to an April 2019 company press release, the drug caused no serious adverse events or changes in common safety measures including vital signs, cardiac function, and laboratory analyses.
					preclinical	(Brice, 2021 #1897)
					Preclinical	NE3107 Impact in Parkinson's Mice Models Leads to a decrease in proinflammatory factors and preserves dopaminergic neurons Reduced iNOS, TNFa, and IL1, b. ↓ LID
CVN766		Schizophrenia, Negative Symptoms		Phase 1
CVN293	Target 06 = KCNK13	Neuroinflammation ALS/FTD		IND enabling:	show NLRP3 reducing efficacy across cellular and slice tissue preparations and demonstrated in vivo efficacy in attenuating the disease progression of the SOD1 (G93A) ALS mouse. CVN293 will enter the clinic initially targeted at ALS
	CD38 (Target 20 LO), Ceri 경험	Neuroprotection AD/PD			CD38 (cluster of differentiation 38), also known as cyclic ADP-ribose hydrolase is a glycoprotein[5] found on the surface of many immune cells (white blood cells), including CD4+, CD8+, B lymphocytes and natural killer cells. CD38 also functions in cell adhesion, signal transduction and calcium signaling.[6] CD38 can function either as a receptor or as an enzyme
	KCNJ6 (Target 18 HtL	Early PD, Dementia
	GPR65 (Target 17 HtL	Neuroinflammation/PD — time pressure

Current Portfolio Status: April 2022

Visible quarterly milestone bar-chart labels (rows top-to-bottom):

• CVN766 (phrenia: Negative symptoms) — GLP studies / CTA / pl safety / ptb CO2 / pll in neg symptoms Sz
• CVN293 (roinflammation ALS/FTD/AD) — LO / Tox / GLP studies / END CTA / pl safety / translational / pll in ALS
• Target 20 (Neuroprotection PD/AD) — H2L / LO / Tox / GLP studies / END CTA / pl safety / ptb PD
• Target 18 (early PD, Dementia) — H2L / LO / Tox / GLP studies / END CTA / pl safety / translational
• Target 17 (Neuroinflammation PD/AD) — H2L / LO / Tox / GLP studies / END CTA / pl safety / translational
• Multiple early targets (AD/ALS/FTD) — Target val / Hit finding (×4 staggered bars)

X-axis quarters: 2021 (Q1-Q4) / 2022 (Q1-Q4) / 2023 (Q1-Q4) / 2024 (Q1-Q4) / 2025 (Q1-Q4) / 2026 (Q1-Q4)

End-state labels visible at right edge: pll in ALS, pll in PD (×2), pl safety / translational (×2)

Key worlds

	assumption
evaluation
scientific confidence
Opportunity, Issues (gap) and risks, mitigation strategy

Team

Function	Team member
Lead	David Kim
	Raj McLaren
	Arthur Simen
	Nancy Goodman
	Emmanuelle Magueur
	Sudipta Bhattacharya
Quantitative Clinical Pharmacology	Lin Xu
Translational Medicine	Lee, Jaewon
Translational Medicine - Biomarkers	Stephen Zicha
Clinical Safety/PV	in process
	in process
	Ravikumar Peri
	Mi-Sook Kim
GMS/PS	Nathan Geething, Andrew Kroetsch
GQ	Ian King
GPLS	Joseph, Yassir
GPLS Pricing and Access	Elizabeth Kinter

Uncertain Spans

location	transcription	uncertainty
Portfolio chart	pl safety / translational / pll in ALS / pll in PD labels	OCR-rendered short labels with pl and pll likely abbreviations for Phl (Phase l) and Phll (Phase ll); preserved verbatim.
Team / left-clipped Function cells	rows for Raj McLaren, Arthur Simen, Nancy Goodman, Emmanuelle Magueur, Sudipta Bhattacharya, Ravikumar Peri, Mi-Sook Kim	the function-column text is clipped at the left edge and not visible in the body crops; preserved as empty cells.