Maze stock increases 55% in one day after reporting favorable phase 1 data for MZE782 and private investment of $150 million
September 12th, 2025 By John Widen
Yesterday was a good day to be a Maze Therapeutics employee or investor with equity in the company.
Maze completed an IPO on the Nasdaq exchange January 31st, 2025 with an opening price of $16.00/share.
The stock dipped to around $8/share in the middle of April (many biotech company stock prices went down
during this period) and was hovering around $16/share at the start of trading yesterday. Maze published
two press releases yesterday informing the public that their newest clinical asset MZE782 for the treatment
of Chronic Kidney Disease (CKD) and Phenylketonuria (PKU) had a positive phase 1 readout AND a group of
private investors paid a premium stock price investing $150 million into the company. Maze Therapeutic’s
stock price closed at $24.80 yesterday, making a 55% increase from the start of the day. I’m sure everyone there will have a little more pep to their step to close out the week.
There is no actual Phase 1 data that has been released to my knowledge, but instead key results from a
randomized, double-blind, placebo-controlled safety and biomarker study involving 112 healthy volunteers.
MZE782 was given orally as a single ascending dose (SAD) and multiple ascending dose (MAD). The SAD doses ranged from
30-960 mg and the MAD range was 120-240 mg BID or 120-270 mg QD.
They also had a group to study the effect of diet and fasting when taking the drug candidate.
The dosing goes quite high but there was not a single serious adverse event (SAE) observed
for the SAD or MAD groups. It seems that MZE782 can be dosed quite high to individuals in
order to demonstrate efficacy in Phase 2, which is a very nice position to be in. Often times,
Phase 1 doses are limited by toxicity or adverse effects that have to be mitigated, which can
reduce the window to show efficacy.
Maze also reported that biomarkers moved in a dose-dependent manner including increased
excretion of phenylalanine (Phe). They specifically report a 39-fold increase in Phe excretion
in urine at the highest dose of 960 mg for the single dose (SAD) and 42-fold increase on Day 7 in
the MAD cohort at the 240 mg dose. Those are quite large changes and it will be interesting to see
exactly how much phenylalanine excretion is required to demonstrate efficacy in patients with phenylketonuria (PKU),
which have increased levels of circulating Phe due to a mutation in phenylalanine hydroxylase (PAH). PAH hydroxylates
Phe to tyrosine (Tyr) and is responsible for metabolism of Phe. Therefore, when this enzyme is non-functional,
increased levels of Phe occur that cause a variety of issues if untreated. These phase 1 data suggest
that MZE782 can lower circulating Phe quite significantly.
Another biomarker readout reported is estimated glomerular filtration rate (eGFR).
Maze reported that filtration rates decreased as expected. Decreasing eGFR in patients with
chronic kidney disease is indicative of worsening disease. However, in this case an initial
decrease in eGFR occurs in other CKD treatments including inhibitors for SGLT2
(sodium-glucose cotransporter 2) and (RAAS Renin-Angiotensin-Aldosterone System).
Initial decrease in eGFR correlates to reducing the rate of decline of kidney function.
I am not an expert here but producing the same result as other approved drugs
to treat CKD is likely a good thing.
The structure of MZE782 has not been disclosed yet but is a small molecule inhibitor
of a neutral amino acid transporter B0AT1 (Broad neutral amino acid transporter 1,
gene name SLC6A19, a.k.a. solute carrier family 6A member 19). B0AT1 is expressed
on the apical membrane of renal and intestinal epithelial cells and, as the name suggests,
transports neutral amino acids. In the intestines B0AT1 is responsible for uptake
of amino acids. In the kidneys the transporter is responsible for reabsorbing amino acids.
Now, based on the Maze Therapeutics phase 1 trial results, inhibiting B0AT1 reduces
levels of Phe and glutamine (Gln).
Maze has four patent applications disclosing inhibitors of B0AT1 (SLC6A19).
Those applications are listed below:
- WO2025049604
- WO2024112830
- WO2024112831
- WO2024081748
These applications were published in short succession.
Two of them were filed on the same day and all of them within a year of each other.
Because they were filed so close together it is difficult to tell what patent application would
include the structure or claims for MZE782 based on timeline. However, all four patent
applications have very similar chemical structures. In Fig. 1 are the
four Markush structures with a representative molecule from each patent application.
The core of the molecule is an indole in three out of the four applications and the last is an indazole.
There are hundreds of molecules exemplified in each patent application. Kudos to the chemistry
team at Maze for producing so many molecules. They also report actual IC50 values instead of potency buckets.
Many of the molecules have similar potencies in the 100-500 nM range. One application stood out, WO2024112831,
which contains the indazole series because the potencies in that application are consistently below 100 nM.
Either way, congratulations to Maze Therapeutics on the favorable phase 1 readout for MZE782.
The biomarker data strongly suggests it can make an impact in patients with PKU and CKD in planned
phase 2 trials set to begin in 2026. Maze Therapeutics has another clinical-stage small molecule asset,
MZE829, which targets ApoL1 (Apolipoprotein L1). The mechanism of action of MZE829 is inhibition of
APOL1-mediated ion transport through pore formation in cell membranes. MZE829 is currently enrolling
for a Phase 2 trial for ApoL1-mediated kidney disease (AMKD, NCT06830629).
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