Bryan MacDonald

Director, Metabolic Disease Discovery Research @QuotientTx, translating somatic variants into therapies, views my own, part-time runner, full-time corgi walker

[Sek Kathiresan MD @skathire]

@VerveTx 3Q earnings:

1. VERVE-102 targeting PCSK9 being tested in Heart-2 trial

*treated 7 patients now across 2 dose levels (0.3 mg/kg and 0.45 mg/kg)
*well tolerated, no serious adverse events, no clinically significant lab abnormalities
*escalation to next dose after planned DSMB
*data disclosure planned in 1H 2025

2. VERVE-201 targeting ANGPTL3 - first patient has been dosed in Pulse-1 trial!

3. Continued progress on pre-clinical LPA product candidate

4. $540M in cash, runway through 2026

5. With two product candidates now in the clinic, 2025 should be an eventful year for Verve's vision 👇

https://t.co/g9ZcJYJg8Q

[Kansas Jayhawks @KUAthletics]

The Lasso Way 👏

[Sek Kathiresan MD @skathire]

Thrilled to announce that @US_FDA has cleared our

*investigational new drug (IND)* application

for VERVE-101

FDA reviewed our hold response which included:
1. interim clinical data from the ongoing heart-1 trial currently being conducted ex-U.S.
2. pre-clinical data to address their questions

Allows us to start heart-1 trial in US to test VERVE-101 in patients living with heterozygous familial hypercholesterolemia

See full release here: https://t.co/mnp0Aqnd3P

$VERV @VerveTx

[Sek Kathiresan MD @skathire]

Idea: 2016
Company: 2018
NHP data: 2020
1st patient dosed: 2022

1st human data for in vivo liver base editing in patients with heterozygous familial hypercholesterolemia and ASCVD

👇🏽

@American_Heart
@VerveTx
$VERV

Stay tuned!

[Sek Kathiresan MD @skathire]

@CircAHA @VerveTx approach to targets:

human genetics: heterozygous & homozygous deficiency -> protection from disease, tolerated & safe

human pharmacology: another Rx against target proven to work in patients

These validation criteria led to prioritization of PCSK9, ANGPTL3, & LPA

[Bryan MacDonald @bryanmac14]

Implications are less to do with blood pressure and more to do with coat color. Direct Corin cleavage of Agouti/ASIP can affect receptor complexes that control production of the dark pigment Eumelanin and the light yellow Pheomelanin. Less Corin = more yellow in the hair shaft.

[Bryan MacDonald @bryanmac14]

Sometimes during early drug development on enzymes, you find interesting new substrates. Sharing our recent bioRxiv where we report a new Corin atrial natriuretic peptide-converting enzyme substrate: Agouti-signaling protein (ASIP) https://t.co/keOjLlzZvr

[Bryan MacDonald @bryanmac14]

Here we identified the precise Corin cleavage site in Agouti-signaling protein (ASIP). Thanks to Nadine Elowe, Colin Garvie, Virendar Kaushik and @patrick_ellinor from CDoT and CVDi @broadinstitute

[Circulation @CircAHA]

Shunkert and Kessler provide #editorial commentary on the potential for a vaccine targeting ADAMTS-7 to prevent atherosclerosis/in-stent restenosis #AHAJournals https://t.co/1PZf3X5FtX

[Sek Kathiresan MD @skathire]

UK's MHRA

has awarded VERVE-101 for Rx of heterozygous familial hypercholesterolemia an

Innovation Passport

under Innovative Licensing & Access Pathway (intended to accelerate time to market & patient access)

https://t.co/UqrO51IkCf

$VERV @VerveTx

[Jimmy Hu @jimmy_k_hu]

Excited to share this preview on three exciting digit regeneration studies from the groups of @JessicaLehoczky @MarianRosL and Freda Miller. https://t.co/6XdKJuEJ9o

[Sek Kathiresan MD @skathire]

Nice graphical abstract from @escardio review on advances in dyslipidemia (L)

@vervetx mission (R)

Three pillars of lipoprotein risk - LDL, TRL, Lp(a)

We are developing a once-&-done medicine for each: PCSK9 (LDL), ANGPTL3 (LDL & TRL), and LPA (Lp(a))

https://t.co/XAYmJXUNw0

[Circulation @CircAHA]

#OriginalResearch: A Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia @QingboX #AHAJournals https://t.co/M6KGRFleFj

[Bryan MacDonald @bryanmac14]

Interesting new paper out from Wei Kong showing positive effects in vivo from anti-ADAMTS7 antibodies raised to the human ADAMTS7 catalytic domain

Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia https://t.co/c3dH2s2oAv

[Sek Kathiresan MD @skathire]

In @CircAHA, we publish today pre-clinical data for VERVE-101

Of note, @American_Heart tells us that for Scientific Sessions '22, this abstract the highest ranked one of all submitted from U.S.

#AHA22

Press release: https://t.co/1bS92wEqtB

Paper: https://t.co/XtL0Y5lzJF

[Sek Kathiresan MD @skathire]

Delighted to announce a

Clinical Trial Authorization (CTA) clearance

by UK MHRA (Medicines and Healthcare products Regulatory Agency)

for VERVE-101

as investigational Rx for patients with heterozygous familial hypercholesterolemia

https://t.co/tCIpNR4NbY

$VERV @VerveTx

[Sek Kathiresan MD @skathire]

Excited to announce today:

development candidate for 2nd program

(VERVE-201 targeting the ANGPTL3 gene)

to treat homozygous FH as well as ASCVD

data to be presented by @amitvkhera @escardio 2022

Press release: https://t.co/R1vvx7m2Ur

Data: https://t.co/HKwOLCupyp

$VERV

[Sek Kathiresan MD @skathire]

Eventful few months
@VerveTx

*VERVE-101 1st patient dosed
*Evolution board, addition of Lonnel Coats & Bo Cumbo
*Add new target for base editing
*Collaboration with Vertex
*Follow-on financing
*Cash runway extended to 2H 2025

$VERV

https://t.co/Bkn49Tlv1E

[Sek Kathiresan MD @skathire]

2018: @VerveTx founded with concept of one-time Rx to lower LDL as low as possible for as long as possible

Today: we are announcing

dosing of *first patient* with VERVE-101,

an in vivo CRISPR base editing medicine

🙏 to patient volunteer

$VERV

https://t.co/ofKyihBN4w

[Sek Kathiresan MD @skathire]

And it’s about to get real 👌🏽

⁦@VerveTx⁩ VERVE-101 Phase 1

https://t.co/CVSoHj3Dhq registration now live

A Study of VERVE-101 in Patients With Familial Hypercholesterolemia and Cardiovascular Disease - Full Text View - https://t.co/CVSoHj3Dhq https://t.co/pf2GQpGQff