UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒ANNUAL REPORT PURSUANT TO SECTION 13
OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2025
or
☐TRANSITION REPORT PURSUANT TO SECTION
13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from __________________________
to __________________________
Commission file number 001-40804
PASITHEA THERAPEUTICS CORP.
(Exact name of registrant as specified in its charter)
State or other jurisdiction of (I.R.S. Employer
incorporation or organization Identification No.)
(Address of principal executive offices) (Zip Code)
Registrant’s telephone number, including
area code: (786)977-3380
Securities registered pursuant to Section 12(b)
of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock, par value $0.0001 per share KTTA The Nasdaq Capital Market
Securities registered pursuant to Section 12(g)
of the Act: None
Indicate by check mark if the registrant is a
well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate by check mark if the registrant is not
required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant
(1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months
(or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements
for the past 90 days. Yes ☒ No ☐
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405
of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes
☒ No ☐
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,”
and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
Emerging growth company ☒
If an emerging growth company, indicate by
check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial
accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant
has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial
reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or
issued its audit report. ☐
If securities are registered pursuant to Section
12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction
of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error
corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s
executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant
is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the common stock, par value $0.0001 per
share (“Common Stock”), held by non-affiliates of the registrant as of the last business day of the registrant’s most
recently completed second fiscal quarter (June 30, 2025) was $5.1 million.
As of March 24, 2026, there were 24,939,948 shares of the registrant’s
Common Stock outstanding. This number does not include 64,053,335 shares of Common Stock issuable upon the exercise of pre-funded warrants
outstanding as of March 24, 2026 (which are immediately exercisable at an exercise price of $0.001 per share of Common Stock, subject
to beneficial ownership limitations).
DOCUMENTS INCORPORATED BY REFERENCE
None.
PASITHEA THERAPEUTICS CORP.
2025 FORM 10-K ANNUAL REPORT
TABLE OF CONTENTS
Page
PART I
ITEM 1. BUSINESS 1
ITEM 1A. RISK FACTORS 27
ITEM 1B. UNRESOLVED STAFF COMMENTS 54
ITEM 1C. CYBERSECURITY 54
ITEM 2. PROPERTIES 54
ITEM 3. LEGAL PROCEEDINGS 54
ITEM 4. MINE SAFETY DISCLOSURES 54
PART II
ITEM 6. [RESERVED] 55
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 60
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 60
ITEM 9A. CONTROLS AND PROCEDURES 61
ITEM 9B. OTHER INFORMATION 61
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 61
PART III
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 62
ITEM 11. EXECUTIVE COMPENSATION 69
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 82
PART IV
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 84
SIGNATURES 86
i
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
This annual report contains
forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities
Exchange Act of 1934, as amended. These statements are generally identified by the use of such words as “may,” “could,”
“should,” “would,” “believe,” “anticipate,” “forecast,” “estimate,”
“expect,” “intend,” “plan,” “continue,” “outlook,” “will,” “potential”
and similar statements of a future or forward-looking nature. These forward-looking statements speak only as of the date of filing this
annual report with the SEC and include, without limitation, statements about the following:
● our limited operating history;
● the success of competing therapies that are or may become available;
ii
● our dependence on third parties;
● our ability to regain and maintain compliance with Nasdaq listing standards;
Because forward-looking statements are inherently subject to risks
and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these
forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may
not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. You should
refer to the “Risk Factors” section of this annual report for a discussion of important factors that may cause our actual
results to differ materially from those expressed or implied by our forward-looking statements. We operate in an evolving environment
and new risk factors and uncertainties may emerge from time to time. It is not possible for management to predict all risk factors and
uncertainties. As a result of these factors, we cannot assure you that the forward-looking statements in this annual report will prove
to be accurate. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained
herein, whether as a result of any new information, future events, changed circumstances or otherwise. You should review the factors and
risks and other information we describe herein and in the other reports we file from time to time with the SEC (as defined below).
iii
PART I
ITEM 1. BUSINESS
Overview
We are a clinical-stage biotechnology company focused on the discovery,
research and development of innovative treatments for RASopathies, MAPK pathway-driven tumors, and other diseases, including central nervous
system (CNS) disorders.
Our Therapeutic Pipeline
We are advancing a pipeline of two therapeutic product candidates,
with a focus on our lead product candidate, PAS-004, a next-generation macrocyclic (as defined below) Mitogen-Activated Protein Kinase
(“MEK”) inhibitor, that we believe may address the limitations and liabilities associated with existing drugs with a similar
mechanism of action. PAS-004 is a small molecule allosteric inhibitor of MEK 1 and 2 (“MEK 1/2”) for potential use in the
treatment of a range of RASopathies, including neurofibromatosis type 1 (“NF1”), a number of MAPK pathway driven tumors, such
as those driven by BRAFv600 mutations and BRAF fusion tumors, amyotrophic lateral sclerosis (“ALS”), among other indications
including ETS2 driven diseases, such as inflammatory bowel disease (“IBD”), primary sclerosing cholangitis and ankylosing
spondylitis.
MEK 1/2 are two of several
protein kinases involved in a signaling cascade, known as the mitogen-activated protein kinase, or MAPK pathway. The MAPK pathway
is an important pathway in cellular biology which has been a frequent target for drug discovery efforts. The MAPK pathway has been implicated
in a variety of diseases, as it functions to drive cell proliferation, differentiation, survival and a variety of other cellular functions
that, when abnormally upregulated, are critical for the formation and progression of tumors, fibrosis and other diseases. MEK inhibitors
block phosphorylation (activation) of extracellular signal-regulated kinases (“ERK”), which can lead to cell death and inhibition
of tumor growth.
Existing MEK inhibitors approved by the U.S. Food and Drug Administration
(the “FDA”) are marketed for a range of diseases, including (i) certain cancers and (ii) symptomatic, inoperable NF1-associated
plexiform neurofibromas (“NF1-PN”). For NF1-PN, Koselugo (selumitinib) and Gomekli (mirdametinib) are FDA approved for adult
and pediatric NF1-PN patients. We believe that current FDA-approved MEK inhibitors have certain limitations, including known toxicities
and high rates of adverse events (“AEs”) that may lead to dose interruptions and/or discontinuations and poor tolerability.
Unlike currently FDA-approved MEK inhibitors, PAS-004 features a macrocyclic structure, a characteristic that we believe improves selectivity,
provides higher oral bioavailability, and offers better metabolic stability. Macrocyclic molecules also provide structural rigidity, enabling
stronger binding with target receptors. PAS-004’s macrocyclic design was specifically developed to improve metabolic stability and
optimize its pharmacokinetic (“PK”) profile. The structure of PAS-004 is distinct from other earlier generation MEK inhibitors
as it maintains critical protein/ligand contacts but does not possess a primary alcohol or hydroxamate functionality, a known metabolic
liability in earlier generation MEK inhibitors. As described in greater detail below, PAS-004 offers a long half-life, a low peak (“Cmax”)
to trough (“Cmin”) drug concentration ratio, and stable steady-state drug levels over time. We believe that sustained suppression
of the MAPK pathway may result in improved efficacy, safety, and a broader therapeutic window (the dosage range of a drug that provides
safe and effective treatment with minimal adverse effects, spanning from the minimum effective concentration to the minimum toxic concentration)
as compared to current FDA-approved MEK inhibitors for NF1-PN, which have shorter half-lives, higher Cmax to Cmin ratios, and require
twice-daily dosing. However, the ultimate safety and efficacy profile of PAS-004 will require clinical testing to be completed.
In December 2023, the FDA cleared our Investigational New Drug application
(the “IND”) for PAS-004 and we received a study may proceed letter for our first-in-human Phase 1 multicenter, open-label
trial of PAS-004 in patients with MAPK pathway-driven advanced tumors with a documented RAS, NF1 or RAF mutation or patients who have
failed BRAF/MEK inhibition (the “FIH Phase 1 Advanced Cancer Study”). We are currently conducting the FIH Phase 1 Advanced
Cancer Study at four clinical sites in the U.S. and three sites in Eastern Europe and expect to complete the FIH Phase 1 Advanced Cancer
Study in 2028. The primary objective of the FIH Phase 1 Advanced Cancer Study is to assess the safety and tolerability of PAS-004 when
administered as a single dose (day 1) and as multiple doses (28-day treatment cycles). Secondary objectives are (i) to characterize the
PK profile of PAS-004 when administered as a single dose and as multiple doses, (ii) to evaluate the pharmacodynamics (“PD”)
effect of PAS-004, (iii) to evaluate the preliminary anticancer activity (efficacy) of PAS-004 per Response Evaluation Criteria in Solid
Tumors (“RECIST”) 1.1 criteria, and (iv) to define the preliminary recommended Phase 2 dose(s) of PAS-004 in adults with MAPK
pathway driven advanced solid tumors.
On September 9, 2024, we announced the successful completion of long-term
chronic toxicology studies for PAS-004. On September 26, 2024, we announced safety, tolerability, pharmacokinetic (PK) and preliminary
efficacy data from the first two cohorts of patients in our FIH Phase 1 Advanced Cancer Study.
To date, we have completed
dose escalation through cohort 8 (45 mg capsule) with a total of 34 patients receiving PAS-004. No patients have discontinued treatment
or interrupted dosing due to treatment-related AEs (“TRAEs”). The AE profile of PAS-004 has been characterized by grade 1
and grade 2 TRAEs, with the most frequently reported of these TRAEs being nausea, vomiting, and diarrhea through the 35-day DLT (as defined
below) period. The interim data through a cut-off date of December 26, 2025, shows that PAS-004 is observed to be well tolerated and supports
PAS-004’s potential favorable safety and tolerability profile.
1
We have observed no dose limiting
toxicities (“DLTs”) in any of the cohorts assessed to date and have not reached the maximum tolerated dose (“MTD”).
As such, we plan to file a protocol amendment to continue dose escalation in the FIH Phase 1 Advanced Cancer Study using our tablet formulation
of PAS-004 in an effort to continue exploring the safety, PK, and early signals of efficacy at higher dose levels of PAS-004. Simultaneously,
a pilot food effect assessment is planned in a subset of patients who agree to participate in this optional component of the study. The
objective of the pilot food effect study is to determine if the PK properties of PAS-004 are impacted when PAS-004 is dosed in a fasted
or fed state. To date, all patients have fasted when being administered PAS-004.
All TRAEs have been either
Grade 1 or Grade 2, with no dose interruptions or modifications, which support PAS-004’s potential favorable safety and tolerability
profile. Additionally, PAS-004 has demonstrated favorable PK properties, including a long half-life of approximately 60 hours, a low peak
to trough (Cmax to Cmin) ratio (ratio below 2) as compared to other FDA approved MEK inhibitors, and linear pharmacokinetics. Additionally,
we have observed preliminary efficacy signals in a subset of advanced cancer patients with BRAF-mutated tumors.
In May 2025, we initiated
our Phase 1/1b multicenter, open-label, dose escalation trial of PAS-004 in adult patients with symptomatic and inoperable, incompletely
resected, or recurrent NF1-PNs (the “Phase1/1b Adult NF1 Trial”). In addition, many of these patients also presented with
cutaneous neurofibromas (“CNs”). The Phase1/1b Adult NF1 Trial is currently being conducted at five clinical trial sites in
the United States, Australia and South Korea.
The primary objective of the
Phase1/1b Adult NF1 Trial is to evaluate the safety and tolerability of PAS-004 when administered for one 28-day treatment cycle in adult
NF1 participants with at least one and up to two additional target PNs that are symptomatic and inoperable, incompletely resected, or
recurrent. Secondary objectives are (i) to identify the recommended Part B dose (“RPBD”) and/or the MTD of PAS-004, (ii) to
characterize the PK and PD profile of PAS-004, (iii) to evaluate the preliminary efficacy of PAS-004 on target PN volume utilizing Response
Evaluation in Neurofibromatosis and Schwannomatosis (“REiNS”) criteria, (iv) to evaluate the preliminary efficacy of PAS-004
on the size, appearance, and associated symptoms of CNs, and (v) to evaluate the impact of PAS-004 on quality of life (“QOL”)
and any physical symptoms attributed to the target PN. Experimental objectives are (i) to evaluate the impact of PAS-004 on QOL and any
physical symptoms attributed to CNs, (ii) to evaluate the impact of PAS-004 on pain and function attributed to PNs, and (iii) to investigate
PAS-004 effects on CN tumor cellular and molecular biology.
The Phase1/1b Adult NF1 Trial
is being conducted in two parts. In Part A (dose escalation phase), following a screening period of up to 28 days, up to 24 eligible participants
will be enrolled sequentially to receive one of four initially planned dose levels of PAS-004 tablets (4 mg, 8 mg, 12 mg, 18 mg) in a
modified 3+3 design. Part A will identify the recommended RPBD. During Part B (expansion phase), approximately 24 eligible participants
will be enrolled in parallel to receive one of two planned dose levels of PAS-004 tablets. Participants will be dosed at the RPBD level
and at a dose level below the RPBD for up to six continuous 28-day treatment cycles. Part B will identify the RP2D.
The initial indications we
plan to seek FDA marketing approval for PAS-004 is the treatment of symptomatic, inoperable NF1-PNs in both adult and pediatric patients.
As such, we aim to conduct a Phase 1 trial for pediatric NF1-PN patients and ultimately complete registrational clinical trials in both
adult and pediatric NF1-PN populations. Pending dialogue with the FDA and other regulatory agencies, we may plan to pursue a second IND
focused on the treatment of NF1-CNs.
Additionally, PAS-004 has
received orphan-drug designation from the FDA for the treatment of NF1.
Our PAS-001 discovery program is in the early stage of development
and aims to develop a brain penetrant small molecule targeting the complement component 4A (“C4A”) for the treatment of schizophrenia.
Recent findings implicate C4A in synaptic loss (fewer connections between nerve cells), which has been shown to occur in schizophrenia.
In humans, structural variation in the complement 4 gene (C4) is an important genetic risk factor for schizophrenia.
During the year ended December
31, 2025, we determined to cease further development of our PAS-003 program for ALS due to several factors including the significant capital,
resources and time required to develop the program, among others.
Our Strategy
Our mission is to develop
innovative therapies to address areas of high unmet medical need, initially in RASopathies for NF1. To achieve our mission, we are executing
a near-term strategy with the following key elements:
2
Overview of Our Lead Program: PAS-004
MAPK Pathway Overview
Signaling pathways describe
a series of biological mechanisms in which a group of molecules work together to control a cell function. A cell receives signals from
its environment when a molecule binds to a specific receptor on or in the cell. This process may be repeated multiple times through the
entire signaling pathway until the last receptor is activated and the cell function is carried out. Abnormal activation of signaling pathways
may lead to diseases.
The MAPK pathway, which
relies upon the Ras/Raf/MEK/ERK signaling cascade, represents a central biological pathway in all human cells that is responsible for
regulating cellular transcription, proliferation and survival. The general structure of the pathway consists of Ras, a small GTPase, and
three downstream protein kinases, Raf, MEK and ERK. ERK 1 and 2 (“ERK 1/2”) are structurally similar protein-serine/threonine
kinases that regulate a variety of cellular processes including adhesion, migration, survival, differentiation, metabolism, proliferation,
transcription, cytoskeletal remodeling and cell cycle progression. MEK 1/2 catalyzes the phosphorylation of ERK 1/2, which is required
for enzyme activation. Phosphorylated ERK 1/2 moves to the nucleus, and in turn activates many transcription factors, regulates gene expression,
and controls various physiological processes, finally inducing cell repair or cell death.
In addition, at the level of Ras, the pathway is negatively regulated
by several proteins, including neurofibromin, the protein encoded by the NF1 gene. Given its direct regulation of ERK,
which directly controls downstream signaling through the MAPK pathway, MEK occupies a pivotal position in this signaling cascade
and represents a rational small-molecule therapeutic target for multiple diseases, including RASopathies (such as NF1), CNS indications
(such as ALS), cardiomyopathies (such as LMNA cardiomyopathy) and oncology indications, where overactivation of the MAPK pathway
contributes to disease onset and/or progression.
Background of MEK Inhibitors
MAPK represents one of the most highly targeted signaling pathways
in drug development. Several allosteric inhibitors of MEK 1/2 are currently in clinical development with six already approved by the FDA;
four for various oncological indications, and two for the treatment of adult and pediatric patients with symptomatic, inoperable NF1-PNs.
A limitation of current FDA approved MEK inhibitors for the treatment of NF1-PNs is their high rates of TRAEs, which may contribute to
dose modifications and discontinuations. These FDA-approved MEK inhibitors for NF1-PN have short half-lives (approximately 6-7 hours)
and require twice per day dosing. Additionally, their PK profiles are characterized by high Cmax to Cmin ratios. This fluctuation in drug
concentration potentially leads to periods of sub-therapeutic effect (around Cmin) and periods around the Cmax level characterized by
a full pathway suppression potentially resulting in AEs.
Our rationale in
developing PAS-004 is to attempt to address these shortcomings to potentially provide patients with improved safety and tolerability
with similar or superior outcomes, as well as a more convenient once per day dosing regimen.
3
RASopathies Overview
RASopathies are a clinically
defined group of genetic syndromes caused by germline mutations in genes that encode components or regulators of the MAPK pathway. These
disorders include neurofibromatosis type 1 (NF1), Noonan syndrome, capillary malformation–arteriovenous malformation syndrome, Costello
syndrome, cardio-facio-cutaneous syndrome, and Legius syndrome. Because of the common underlying MAPK pathway dysregulation amongst all
of these syndromes, RASopathies exhibit numerous overlapping phenotypic features, including CNS abnormalities. The MAPK pathway plays
an essential role in regulating various cell cycle functions, which are critical to normal human development. Therefore, we believe there
is a strong scientific rationale for targeting the MAPK pathway with small-molecule therapeutics to treat various RASopathies.
Neurofibromatosis type 1 (NF1) Overview
The initial indication we plan to seek marketing approval for PAS-004
is the treatment of NF1-PN. NF1 is a RASopathy and part of a group of conditions known as neurocutaneous disorders, conditions that affect
the skin and the CNS. NF1 affects approximately one in 3,000 newborns throughout the world, with approximately 114,000 patients living
in U.S. with NF1.
NF1 arises from mutations
in the NF1 gene which encodes the tumor suppressor neurofibromin. Loss of NF1 function leads to loss of neurofibromin activity, leading
to Ras being locked in its active confirmation, which stimulates MEK, and then ERK activity.
NF1 is characterized by multiple
café au lait (light brown) skin spots and neurofibromas (small benign growths) on or under the skin, and/or freckling in the armpits
or groin. Individuals with NF1 may have other manifestations of the disorder, including cardiac malformations, cardiovascular disease,
vasculopathy, hypertension, vitamin D deficiency, brain malformations, and seizures. About 50% of people with NF1 also have learning disabilities.
Softening and curving of bones, and curvature of the spine (scoliosis) may occur in some patients with NF1. Occasionally, tumors
may develop in the brain, on cranial nerves, or on the spinal cord. NF1 is usually diagnosed during childhood.
Throughout their lifetime,
about 30% to 50% of NF1 patients progress to develop plexiform neurofibromas (“PNs”), which are tumors that grow in an infiltrative
pattern along the peripheral nerve sheath and can cause severe disfigurement, pain and functional impairment. In rare cases NF1-PN may
be fatal. NF1-PN are most often diagnosed within the first twenty years of life. These tumors are characterized by aggressive growth,
which is typically more rapid during childhood. While NF1-PN are initially benign, these tumors can undergo malignant transformation,
leading to malignant peripheral nerve sheath tumors (“MPNST”). NF1 patients have an 8% to 13% lifetime risk of developing
MPNST, a diagnosis that carries a 12-month survival rate of under 50%. In addition to MPNST, NF1 patients are at an increased risk of
developing other malignancies, including breast cancer and gliomas.
Until recently, the only treatment
option for NF1-PN was the surgical removal of the tumors. However, because NF1-PN arise from nerve cells and grow in an infiltrative pattern,
it is challenging to successfully resect tumors and surgery can lead to severe comorbidities, such as permanent nerve damage. Patients
that are ineligible for surgery or those who have had a recurrence post-surgery are often treated with a variety of off-label therapies.
Among these off-label therapies are various systemic treatments, such as chemotherapy and immunotherapy, which have not been shown to
consistently confer a clinical benefit. Given that NF1-PN is driven by dysregulation in the MAPK pathway, MEK inhibitors have emerged
as the only FDA approved therapy for the treatment of inoperable NF1-PNs.
Additionally, over 95% of
NF1 patients develop cutaneous neurofibromas (“CNs”), which are considered one of the hallmarks of the disease.
CNs are a neoplasm of peripheral
nerve Schwann cells that present as a soft nodule in the dermis of the skin at virtually any location in the body. Despite their benign
nature, people with NF1 consider CNs to be the most burdensome feature of the disease. Physical symptoms include irritation, pain, and
itching. Improper drying after wetting may lead to other complications including maceration, skin breakdown, and superficial infections.
Individuals may have hundreds to thousands of CNs over the body leading to physical disfigurement. CNs are linked to a lower quality of
life due to feelings of embarrassment, interference with daily activities and adverse social implications. People with NF1 may suffer
from lower socioeconomic status as a result of their lower self-esteem and risk aversion, and many of those with NF1 suffer from major
depressive disorder likely contributed by their CN burden.
Physical removal or destruction
has been the mainstay of therapy.
4
Limitations of Current Standard of Care
Koselugo (selumetinib), a MEK inhibitor, was first approved by the
FDA in April 2020 for NF1 pediatric patients two years of age and older who have symptomatic, inoperable PNs based on results from the
SPRINT trial, a Phase 2 registrational trial. In November 2025, Koselugo was approved by the FDA for adult NF1 patients with symptomatic,
inoperable PNs based on results from the KOMET study, a randomized, placebo-controlled, parallel, double-blind Phase 3 study. In February
2025, Gomekli (mirdametinib) was approved by the FDA for adult and pediatric patients aged two and older with NF1 who have symptomatic
PNs not amenable to complete resection based on clinical results from the ReNu Phase 2b clinical trial. In addition to Koselugo and Gomekli,
we are aware of other MEK inhibitors in clinical trials for this indication, as well as the off-label use of other drugs, such as bevacizumab,
for the treatment of NF1.
We believe that Koselugo,
Gomekli and other earlier generation MEK inhibitors approved for indications other than NF1 suffer from limitations, such as known toxicities,
high rates of drug discontinuation, limited efficacy and a dosing schedule that requires dosing twice a day. We believe that this creates
a significant market opportunity for a next-generation MEK inhibitor that addresses these shortcomings, has a PK and tolerability profile
suitable for long-term once-a-day or less dosing and that can arrest or reverse tumor growth.
There are no therapies approved by the FDA for the treatment of NF1-CNs.
Preclinical Profile and Mechanism of Action
of PAS-004
PAS-004 is a next-generation
MEK inhibitor that was rationally designed to have a macrocyclic structure by taking into consideration the metabolic liabilities of earlier
generation MEK inhibitors. The structure of PAS-004 is distinct from other earlier generation MEK inhibitors as it maintains critical
protein/ligand contacts but does not possess a primary alcohol or hydroxamate functionality, a known metabolic liability in earlier generation
MEK inhibitors. It is generally observed that macrocyclic scaffolds improve drug-like properties including target binding, selectivity,
and oral bioavailability.
PAS-004 has displayed promising
PK properties in IND-enabling toxicology studies of both rats and dogs. In these toxicology studies, PAS-004 has demonstrated a half-life
of 11.5 hours in rats and 52 hours in dogs.
Preclinical Studies Overview
In vitro Preclinical Studies of PAS-004
In a screen of 99 protein
kinases, a single high dose of PAS-004 (10 μM) was used to assess kinase inhibition specificity. This assay demonstrated that PAS-004
is a strong inhibitor of only the MEK 1 (~95%) and MEK 2 (>99%) kinases.
In an unpublished preclinical
study, the effects of PAS-004 were compared to selumetinib in tests for the ability to inhibit the growth of three NF1 mutant neurofibroma-derived
Schwann cell lines, the tumorigenic cell of origin for NF1-PN, and two human wild-type Schwann cell lines. Cells were treated for 48 hours
and all PAS-004 treated cell lines showed dose-dependent growth inhibition, with 60-80% growth inhibition in the three neurofibroma-derived
NF1 mutant cell lines and less than 20% inhibition of the wild-type cell lines tested. Growth inhibition with PAS-004 was greater than
the maximal growth inhibition seen with equivalent doses of selumetinib. In addition, the inhibition did not plateau at the highest doses
used in the study, compared to a plateau effect with selumetinib.
Additionally, PAS-004 was
compared to selumetinib in an in vitro potency assay. Western blots from this unpublished preclinical study showed that cells treated
with PAS-004 demonstrated greater reduction in ERK 1/2 phosphorylation as compared to cells treated with selumetinib.
We believe these in vitro
preclinical results support PAS-004’s favorable potency and dose-dependent inhibitory activity against cellular proliferation in
NF1 deficient Schwann cells, demonstrating a profile that appears similar to selumetinib, an FDA approved MEK inhibitor.
In vivo Preclinical Studies of PAS-004
In an unpublished preclinical
study, the effects of PAS-004 were assessed in the in vivo Colo-205 xenograft tumor model, a common mouse model used for preclinical
therapies. Results showed that PAS-004 dosed at 5 mg/kg once daily reduced tumor volume. The magnitude of tumor volume reduction was similar
to selumetinib dosed at 25mg/kg, twice daily, as published in Molecular Cancer Therapeutics in 2007.
5
In an unpublished preclinical
pilot study, PAS-004 was tested for tolerability and preliminary biological efficacy in a genetically engineered mouse model of NF1-PN.
These mice were engineered to develop plexiform neurofibromas that closely phenocopy the human tumors by four months of age with
100% penetrance. In this pilot study, selumetinib was administered in a parallel group, which served as a positive control. Both PAS-004
and selumetinib were administered as single-agents to six mice per group. PAS-004 was administered at 10 mg/kg once daily and selumetinib
was administered at the established maximum tolerated dose of 10 mg/kg, twice daily. Treatment began when the mice reached four months
of age and was continued for 12 weeks or until death. Mice were monitored for signs of toxicity, as well as survival. Results demonstrated
that both PAS-004 and selumetinib showed similar toxicity profiles and both PAS-004 (p=0.0123) and selumetinib (p=0.0048) significantly
reduced the tumor size compared to vehicle-treated mice based on statistical analysis using uncorrected Fisher’s least significant
difference.
We believe the results from
this preclinical pilot study illustrate that PAS-004 may be effective in reducing tumor burden of NF1-associated plexiform neurofibromas.
When administered at 10 mg/kg once daily, PAS-004 and selumetinib, which was dosed at 10mg/kg twice daily, demonstrated similar results.
We believe that the longer half-life of PAS-004, as compared to selumetinib, could potentially enhance efficacy by allowing more sustained
MEK/ERK signaling inhibition. Additionally, it may allow for longer dosing intervals, such as a once-daily regimen, compared to the twice-daily
dosing required for selumetinib.
Mutations in the LMNA gene,
which encodes nuclear lamins A and C, cause diseases affecting various organs, including the heart. Studies have found that the ERK 1/2
kinase branches of the MAPK signaling pathway were abnormally hyperactivated prior to the onset of significant cardiac impairment.
PAS-004 was studied in the
LMNA-cardiomyopathy LmnaH222P/H222P mouse model, a validated model of cardiomyopathy caused by LMNA mutations in humans. In
this study, male mice were orally administered placebo, PAS-004 at 3 mg/kg/day or PAS-004 at 6 mg/kg/day starting at 14 weeks of age when
symptoms of cardiomyopathy were present. Results of this preclinical study were published in Bioorganic & Medicinal Chemistry
in 2017 and are summarized as follows:
In unpublished preclinical
in vivo studies, PAS-004 was tested for anti-tumor efficacy in NRAS mutation cancer xenograft models. In the first study, PAS-004
exhibited dose-dependent anti-tumor efficacy in the lung cancer NCI-H1299 cell-line-derived xenograft model. PAS-004 at dose levels of
10 mg/kg and 5 mg/kg, once daily, significantly inhibited tumor growth as compared to vehicle control. The anti-tumor efficacy of PAS-004,
when taken at equivalent doses, was shown to be superior to that of binimetinib and selumetinib. In the second study, PAS-004 exhibited
dose-dependent anti-tumor efficacy in the liver cancer xHepG2 cell-line-derived xenograft model. PAS-004 at dose levels of 10 mg/kg and
5 mg/kg, once daily, produced significant antitumor activities as compared to vehicle control. The anti-tumor efficacy of PAS-004, when
taken at equivalent doses was shown to be similar to that of binimetinib and superior to that of selumetinib.
PAS-004 has demonstrated dose-dependent
response in vivo across several preclinical cancer, LMNA cardiomyopathy and NF1-PN models.
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Toxicology Studies
28-day toxicological studies were performed in both rats and dogs under
good laboratory practices (“GLP”) on PAS-004 by WuXi AppTec (Suzhou) Co., Ltd. and demonstrated a sufficient safety and toxicology
profile of PAS-004 to support our IND with the FDA. Additionally, we have completed repeat dose toxicity and toxicokinetic studies in
Sprague Dawley rats of up to 26 weeks’ duration and in Beagle dogs up to 39 weeks’ duration with 14 or 28-day recovery periods
to support chronic dosing of PAS-004.
Additional Indications: ETS2 Driven Diseases
A 2024 Nature publication
titled “A disease-associated gene desert directs macrophage inflammation through ETS2” demonstrated that the ETS2 gene is
a central regulator for multiple inflammatory functions in human macrophages and that ETS2 has a key pathogenic role in IBD. Further,
this publication identified that MEK inhibitors as a class are the strongest known ETS2 inhibitors, providing potent anti-inflammatory
activity and that MEK inhibition reduced inflammatory cytokine release to similar levels as infliximab, an anti-TNF antibody that is widely
used for the treatment of IBD. Blocking ETS2 signaling through MEK 1/2 inhibition was showed to affect multiple cytokines, including TNF
and IL-23, which are targets of existing therapies. Based on this publication, we tested PAS-004 in pre-clinical models of ETS2 signaling
at the Francis Crick Institute in London, U.K.
Unpublished results from this in vitro study demonstrated that
PAS-004 provides superior inhibition of ETS2-driven inflammatory responses compared to selumetinib in a human macrophage model of chronic
inflammation that mimics the inflammatory milieu seen in IBD. RNA sequencing was used to measure gene expression, with PAS-004 consistently
outperforming selumetinib across all tested doses (0.01 μM, 0.1 μM, and 1 μM), showing greater downregulation of ETS2 target
genes, as well as experimentally validated MEK1/2 pathway genes. These data suggest more robust and durable MEK inhibition by PAS-004
under inflammatory conditions. PAS-004 significantly reduced ETS2-dependent functions such as cytokine production, phagocytosis, and reactive
oxygen species (ROS) generation, all known to be central to chronic inflammation. Gene Set Enrichment Analysis revealed that PAS-004’s
effects more closely mirrored ETS2 knockout profiles, with a higher normalized enrichment score (-3.96 vs -3.56) and greater statistical
significance (1.2 x 10−250 vs 3.7 x 10−74) as compared to selumetinib.
Completion of GMP-Compliant Manufacturing
In June 2023, we announced the successful completion of manufacturing
the GMP-compliant Phase 1 clinical supplies of the active pharmaceutical ingredient (“API”) of our lead product candidate
PAS-004. Utilizing this drug substance, we have manufactured the drug product in capsule form that we are utilizing in our ongoing FIH
Phase 1 Advanced Cancer Study. In 2024, we completed a second batch of API and we have manufactured the drug product in tablet formulation
to support our ongoing Phase 1/1b Adult NF1 Trial. In 2025, we improved the synthesis process of PAS-004 and have optimized the manufacturing
process of API for commercial scale. In 2026, we plan to complete manufacturing of a third batch of API and drug product in tablet formulation
to support our ongoing clinical trials and planned non-clinical studies. Throughout 2025 we continued to improve the synthesis process
of PAS-004, and we believe we have further optimized the manufacturing process for commercial scale.
Clinical Development Overview
We are currently conducting
two ongoing global clinical trials of PAS-004. Our clinical development plan for PAS-004 is to continue our Phase 1/1b clinical trial
in adult patients with NF1-PN followed by pediatric NF1-PN patients and ultimately complete registrational clinical trials in these patient
populations, which are the initial indications that we plan to seek marketing approval of PAS-004 for. In addition, we plan to analyze
the NF1-CN results in the ongoing Phase 1/1b Adult NF1 Trial and may engage the FDA and necessary regulatory agencies for a separate clinical
development path for the treatment of NF1-CN.
FIH Phase 1 Advanced Cancer Study
The FIH Phase 1 Advanced Cancer Study is a multicenter open-label study
designed to evaluate the safety, tolerability, PK, PD, and preliminary efficacy of PAS-004 in cancer patients with MAPK pathway driven
advanced solid tumors. Patients are being enrolled across four clinical sites in the U.S. and three clinical sites in Eastern Europe (Bulgaria
and Romania) into dosing cohorts under a modified 3+3 dose escalation study design. If the first three patients enrolled into a dosing
cohort reach the end of the first 28-day treatment cycle on day 35 without experiencing a DLT, following a review of safety, PK, and PD
data by the safety committee, enrollment into the next highest dosing cohort begins. If two or more of the first three patients experience
a DLT by day 35, dose-escalation will stop and cannot proceed at or above the current dose level. However, if one of the first three patients
enrolled into a dosing cohort experiences a DLT by day 35, an additional three patients will be enrolled into the dosing cohort (six patients
total). If only one of six patients experiences a DLT by day 35, following review of safety, PK and PD by the safety committee, enrollment
into the next highest dose level begin; however, if two or more of the six patients experience a DLT, dose escalation will stop, and the
prior dose level will be declared the MTD. Participants have sequentially received one of eight planned dose levels of PAS-004 in capsule
formulation (2 mg, 4 mg, 8 mg, 15 mg, 22 mg, 30 mg, 37 mg and 45 mg) taken orally. Additionally, we have completed a dosing cohort using
a 4 mg tablet formulation of PAS-004. PAS-004 is administered as a single dose on day 1, followed by a 7-day observation period, before
initiating continuous 28-day treatment cycles of PAS-004.
To date, we have completed
dose escalation through cohort 8 (45 mg capsule), with a of a total of 34 patients receiving PAS-004. No patients have discontinued treatment
or interrupted dosing due to TRAEs). The AE profile of PAS-004 has been characterized by grade 1 and grade 2 TRAEs, with the most frequently
reported of these TRAEs being nausea, vomiting, and diarrhea through the 35-day DLT period. The interim data shows that PAS-004 is observed
to be well tolerated and support PAS-004’s potential favorable safety and tolerability profile.
We have observed no DLTs in
any of the cohorts assessed to date and have not reached the MTD. As such, we have filed a protocol amendment to continue dose escalation
in the FIH Phase 1 Advanced Cancer Study using our tablet formulation of PAS-004 in an effort to continue to explore the safety, PK, and
early signals of efficacy at higher dose levels of PAS-004. Simultaneously, a pilot food effect assessment is planned in a subset of patients
who agree to participate in this optional component of the study. The objective of the pilot food effect study is to determine if the
PK properties of PAS-004 are impacted when PAS-004 is dosed in a fasted or fed state. To date, all patients have fasted when being administered
PAS-004.
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Interim PK results have
demonstrated a half-life of approximately 60 hours for PAS-004, dose proportionality and linear PK. At steady-state, little
fluctuations in drug concentrations are observed with a ratio of Cmax to Cmin below 2. Additionally, we have observed preliminary
efficacy signals in a subset of advanced cancer patients with BRAF-mutated tumors.
We plan to provide additional
interim data throughout 2026 and currently expect to complete the FIH Phase 1 Advanced Cancer Study in 2028.
Phase 1/1b Adult NF1 Trial
The Phase 1/1b Adult NF1 Trial
is a multicenter, open-label study designed to evaluate the safety, tolerability, PK and PD of PAS-004, in adult participants with NF1
with symptomatic and inoperable, incompletely resected, or recurrent PNs. This trial is being conducted at five clinical sites in the
U.S., Australia, and South Korea. We opened our first clinical trial site in Australia in May 2025 and dosed the first patient in July
2025.
The primary objective of the
study is to evaluate the safety and tolerability of PAS-004 when administered for one 28-day treatment cycle in adult NF1participants
with at least one and up to two additional target PNs that are symptomatic and inoperable, incompletely resected, or recurrent. Secondary
objectives are (i) to identify the RPBD or MTD of PAS-004, (ii) to characterize the PK and PD profile of PAS-004, (iii) to evaluate the
preliminary efficacy of PAS-004 on target PN volume, (iv) to evaluate the preliminary efficacy of PAS-004 on the size and appearance,
and associated symptoms of CNs, and (v) to evaluate the impact of PAS-004 on QOL and any physical symptoms attributed to the target PN.
Experimental objectives are (i) to evaluate the impact of PAS-004 on QOL and any physical symptoms attributed to CNs, (ii) to evaluate
the impact of PAS-004 on pain and function attributed to PNs, and (iii) to investigate PAS-004 effects on CN tumor cellular and molecular
biology.
The primary endpoints are (i) the evaluation of DLTs, (ii) the evaluation
of all AEs, (iii) the evaluation of AEs leading to interruption or discontinuation of PAS-004, and (iv) the evaluation of cardiac and
visual function, hematology and clinical chemistry laboratory parameters. The secondary endpoints are (i) the evaluation of PK parameters,
(ii) the evaluation of PD parameters including percentage of ERK phosphorylation inhibition from baseline in peripheral blood mononuclear
cells (“PBMCs”), (iii) the evaluation of clinical benefit rate in terms of complete response, partial response, stable disease,
and progressive disease over time on magnetic resonance imaging (“MRI”) with volumetric analysis using REiNS criteria, (iv)
the evaluation of the best objective response rate over time on MRI with volumetric analysis using the REiNS criteria, (v) the evaluation
of time to maximal response on MRI with volumetric analysis using the REiNS criteria, (vi) the evaluation of CN appearance and size metrics
over time using photography and quantitative measurements, (vii) the evaluation of changes from baseline in physical functioning using
the Patient-Reported Outcomes Measurement Information System (PROMIS), Physical Function (PF) assessment, and in QOL using the Plexi-QOL
survey.
Following a screening period
of up to 28 days, up to 24 eligible participants in Part A will be enrolled sequentially to receive one of four planned dose levels of
PAS-004 (4 mg, 8 mg, 12 mg, and 18 mg) tablets to be taken orally once daily.
The dose escalation phase
(Part A) is following a modified 3+3 study design. At the first planned dose level of 4 mg (day 1), participants will be provided with
PAS-004 to be taken once daily during a continuous 28-day treatment cycle. If the first three participants enrolled into each dosing cohort
complete the 28-day treatment cycle without experiencing a DLT, following a review of safety and available PK and PD data by the safety
review committee, enrollment into the next higher dosing cohort will begin. If two or more of the first three participants experience
a DLT, dose-escalation will stop and cannot proceed at or above that current dose level. However, if only one of the first three participants
enrolled into a dosing cohort experiences a DLT by day 28, an additional three participants will be enrolled into the same dosing cohort
(six participants in total). If no additional participants develop a DLT, enrollment into the next highest dose level may begin after
review of safety and available PK and PD data by the safety review committee for all six participants. The dose escalation can be adjusted
by the safety review committee based on the safety considerations. However, if two or more of the six participants experience a DLT, dose
escalation will stop, and the prior dose level will be declared the MTD. The RPBD will be identified as the dose level where at least
three participants in a dosing cohort demonstrate optimal ERK phosphorylation inhibition and 0 of 3 participants or greater than 1 of
6 participants experience a DLT. The RPBD will be a dose level at or below the MTD.
Participants in Part A will
be treated at their assigned dose level of PAS-004 for six treatment cycles. Each 28-day treatment cycle consists of once daily continuous
dosing. Part A of the study also includes an optional treatment extension period of up to an additional six treatment cycles (up to 12
cycles in total). If the RPBD for Part B has not yet been selected, participants in Part A who have completed six treatment cycles may
continue treatment for up to an additional six treatment cycles in Part A. This is to allow qualifying participants to continue in Part
A without treatment interruption before enrolling in Part B and for continued safety data collection at the dose levels evaluated in Part
A.
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Participants in Part A will
have their PNs and up to seven CNs measured at baseline. PNs will be measured on MRI at baseline and at the end of cycle 4 and cycle 6
as well as cycle 9 and cycle 12 for participants in the optional treatment extension period. CNs will be measured using digital calipers
and two-dimensional photography at baseline and at the end of cycle 1, cycle 4, cycle 6, as well as cycle 9 and cycle 12 for participants
in the optional treatment extension period.
To date, we have completed
enrollment and dosing of three patients in each of the initial four cohorts in Part A. All patients currently remain on trial with the
opportunity to remain on study for up to 12 cycles. We expect to complete Part A by the end of 2026 and move to Part B in 2027 following
dialogue with the FDA and other regulatory agencies. We expect to complete Part B of the trial in 2028.
Our clinical development plan
for PAS-004 is to continue our Phase 1/1b clinical trial in adult patients with NF1-PN followed by pediatric NF1-PN patients and ultimately
complete registrational clinical trials in these two age indications, which are the initial indications that we plan to seek marketing
approval of PAS-004 for. In addition, we plan to analyze the NF1-CN results and may engage the FDA for a separate development path for
NF1-CN.
Overview of Our Discovery Program: PAS-001
Schizophrenia Overview
Schizophrenia is a chronic
and disabling psychiatric illness characterized by positive psychotic symptoms, such as delusions and hallucinations, negative symptoms,
such as social withdrawal and amotivation, and impairment in cognitive domains, including attention, working memory, verbal learning and
executive function. According to the World Health Organization (“WHO”) schizophrenia affects up to 24 million people in the
world. Schizophrenia has a low lifetime prevalence of about 1%, however the burden of the disease is substantial. Schizophrenia is a leading
cause of adult disease burden and has been ranked 12th in the top global causes of disability for the last decade, leading to substantial
healthcare and societal costs, with annual associated costs in the U.S. estimated to be more than $150 billion.
Current pharmacological treatments
for schizophrenia all act on dopamine D2 receptors. Although they are effective in reducing positive symptoms, they have little effect
on both cognitive and negative symptoms. Furthermore, up to 30% of patients show only partial benefit with antipsychotics and have treatment
resistant schizophrenia. This highlights the need for new therapeutic strategies.
Despite extensive research,
the molecular etiology remains unknown. The current dopamine hypothesis postulates that excessive striatal dopamine transmission and reduced
frontal dopamine stimulation underlie the pathophysiology of positive and negative symptoms, respectively. However, converging lines of
genetic, epidemiological and clinical evidence indicate that inflammatory pathways are also altered in schizophrenia. More recently, a
leading hypothesis proposes that synaptic terminal loss is central to the pathophysiology of schizophrenia, leading to impaired cortical
function, and symptoms, including cognitive impairments.
Scientific Background and Rationale for Targeting C4A for the Treatment
of Schizophrenia
The complement system is a
group of proteins found in both the blood and the CNS. In the brain, the complement system plays in almost every aspect of normal brain
development, including neurogenesis, neuronal migration and synaptic refinement, and is now also recognized as a signaling cascade that
facilitate microglial removal of synapses. Microglia are phagocytes residing in the CNS. Unlike other phagocytes, which primarily function
in immunity, microglia are heavily involved in shaping and supporting brain tissue and are key modulators of neuronal development.
There are nine major complement proteins, labeled C1 through C9. Complement protein C4 is the only complement protein that has two different
isotypes encoded by two different genes: C4A and C4B.
According to the synaptic
pruning hypothesis, schizophrenia is thought to arise from a faulty pruning process and excessive synaptic elimination.
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The largest genome-wide association
study (GWAS) in schizophrenia in 2014 identified 128 independent associations spanning 108 conservatively defined loci that meet genome-wide
significance. The most strongly associated GWAS locus is located in the extended Major Histocompatibility Complex (MHC) region on chromosome
6. This locus contains multiple copies of two closely related genes that codes for variants of C4: C4A and C4B. Their analyses revealed
that C4A copy numbers, as well as other structural variance leading to increased C4A mRNA expression, to a large degree explained schizophrenia
risk originating from this locus. This variant remains the strongest polygenic risk factor for schizophrenia identified to date, making
C4A the first gene linked to a specific mechanism underlying the disease. Importantly, schizophrenia risk was not influenced by copy numbers
of the closely related C4B gene.
Animal models of increased
C4A expression show reduced levels of synaptic proteins and increased phagocytosis of synaptic terminals by microglia. Moreover, preclinical
models showed C4A overexpression leads to reduced neurotransmission in prefrontal cortical neurons, reduced social interaction and impaired
memory, which mimic similar abnormalities seen in schizophrenia patients. Finally, excessive microglial synapse elimination has been observed
in schizophrenia patient-derived neural cultures. Post-mortem brain analyses showed that C4A is expressed at significantly higher levels
in people with schizophrenia than controls. C4A levels in cerebro-spinal fluid (“CSF”) have shown to be elevated in patients
with schizophrenia relative to matched controls and correlates with CSF measurements of synapse density. C4A levels have also been found
to be elevated in plasma in schizophrenia, and higher levels predict poorer outcomes in first episode patients.
Several other studies in scientific
journals have also reported increased complement gene expression, protein concentration, and overall activity in the serum or plasma of
schizophrenia cases compared to controls. Further, a 2020 study published in Brain, Behavior and Immunity, found that C4A was overexpressed
in the dorsolateral prefrontal cortex, parietal cortex, superior temporal gyrus and associative striatum of patients with schizophrenia
and that C4A expression was not altered in the peripheral tissues of schizophrenia patients. Further, the study found lifelong C4Aoverexpression
in the brain of schizophrenia patients. Taken together, this evidence has led to the hypothesis that C4A may play an important role in
the pathophysiology of schizophrenia.
We are currently developing a brain-penetrant small molecule able to
down regulate C4A, for the systemic treatment of schizophrenia. To our knowledge, no other company is exploring this potentially important
target. To date, we have created over 100 analogs of our 20 priority hits as provided via our past screening partnership with Evotec.
In addition, we have used assays to assess C4 selectivity. We have prioritized several analogs for PK testing in mice. To date, we have
demonstrated C4 selectivity in astrocytes and are expanding into additional cell types in vitro. We are continuing to conduct additional
work for target deconvolution to identify a lead candidate. Our goal is to continue screening and proceeding with early development of