UNITED STATES
SECURITIES AND EXCHANGE
COMMISSION
Washington, D.C. 20549
FORM 10-K
☒ANNUAL
REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended
December 31, 2025
☐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 001-40582
UNICYCIVE THERAPEUTICS,
INC.
(Exact name of registrant
as specified in its charter)
(Address of principal executive offices) (Zip Code)
Registrant’s telephone number, including
area code: (650)351-4495
4300 El Camino Real, Suite 210
Los Altos, CA 94022
(Former name or former address, if changed since last report)
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 $0.001 per share UNCY The Nasdaq Stock Market, LLC
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 filter ☐ Accelerated filter ☐
Non-accelerated filter ☒ 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 by Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the voting stock and non-voting common
equity held by non-affiliates of the registrant as of the last business day of the registrant’s most recently completed second fiscal
quarter ended June 30, 2025 was $64,310,247 based upon the closing price of the registrant’s common stock of $4.77 on The Nasdaq
Capital Market as of that date.
The number of shares of common stock outstanding as of March 30, 2026
was 25,237,782.
DOCUMENTS INCORPORATED BY REFERENCE
Specified portions of the registrant’s
proxy statement, which will be filed with the Securities and Exchange Commission pursuant to Schedule 14A in connection with the registrant’s
2026 Annual Meeting of Stockholders (the “2026 Proxy Statement”), are incorporated by reference into Part III of this Annual
Report on Form 10-K. Except with respect to information specifically incorporated by reference in this Annual Report, the 2026 Proxy
Statement is not deemed to be filed as part hereof.
Table of Contents
Page
Part I 1
Item 1. Business 1
Item 1A. Risk Factors 39
Item 1B. Unresolved Staff Comments 70
Item 1C. Cybersecurity 70
Item 2. Properties 71
Item 3. Legal Proceedings 71
Item 4. Mine Safety Disclosures 71
Item 6. [Reserved] 72
Item 7A. Quantitative and Qualitative Disclosures about Market Risk 80
Item 8. Financial Statements and Supplementary Data F-1
Item 9A. Controls and Procedures 81
Item 9B. Other Information 81
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 81
Part III 82
Item 10. Directors, Executive Officers and Corporate Governance 82
Item 11. Executive Compensation 82
Item 14. Principal Accountant Fees and Services 82
Item 15. Exhibit and Financial Statement Schedules 83
Signatures 85
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CAUTIONARY NOTE ON FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking
statements which are made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended (the “Securities
Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may
be identified by such forward-looking terminology as “may,” “should,” “expects,” “intends,”
“plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,”
“continue” or the negative of these terms or other comparable terminology. Our forward-looking statements are based on a
series of expectations, assumptions, estimates and projections about our company, are not guarantees of future results or performance
and involve substantial risks and uncertainty. We may not actually achieve the plans, intentions or expectations disclosed in these forward-looking
statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking
statements. Our business and our forward-looking statements involve substantial known and unknown risks and uncertainties, including
the risks and uncertainties inherent in our statements regarding:
● our projected financial position and estimated cash burn rate;
● our estimates regarding expenses, future revenues, and capital requirements;
● our ability to continue as a going concern;
● our need to raise substantial additional capital to fund our operation;
● the success, cost, and timing of our clinical trials;
● our dependence on third parties in the conduct of our clinical trials;
● the results of market research conducted by us or others;
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● our reliance on third-party suppliers and manufacturers;
● the success of competing therapies and products that are or become available;
All of our forward-looking statements are as
of the date of this Annual Report on Form 10-K only. In each case, actual results may differ materially from such forward-looking information.
We can give no assurance that such expectations or forward-looking statements will prove to be correct. An occurrence of, or any material
adverse change in, one or more of the risk factors or risks and uncertainties referred to in this Annual Report on Form 10-K or included
in our other public disclosures or our other periodic reports or other documents or filings filed with or furnished to the U.S. Securities
and Exchange Commission (the “SEC”) could materially and adversely affect our business, prospects, financial condition, and
results of operations. Except as required by law, we do not undertake or plan to update or revise any such forward-looking statements
to reflect actual results, changes in plans, assumptions, estimates or projections or other circumstances affecting such forward-looking
statements occurring after the date of this Annual Report on Form 10-K, even if such results, changes, or circumstances make it clear
that any forward-looking information will not be realized. Any public statements or disclosures by us following this Annual Report on
Form 10-K that modify or impact any of the forward-looking statements contained in this Annual Report on Form 10-K will be deemed to
modify or supersede such statements in this Annual Report on Form 10-K.
This Annual Report on Form 10-K may include market
data and certain industry data and forecasts, which we may obtain from internal company surveys, market research, consultant surveys,
publicly available information, reports of governmental agencies and industry publications, articles, and surveys. Industry surveys,
publications, consultant surveys and forecasts generally state that the information contained therein has been obtained from sources
believed to be reliable, but the accuracy and completeness of such information is not guaranteed. While we believe that such studies
and publications are reliable, we have not independently verified market and industry data from third-party sources.
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RISK FACTOR SUMMARY
Our business is subject to numerous risks and
uncertainties, including those highlighted in the section titled “Risk Factors,” that represent challenges that we face in
connection with the successful implementation of our strategy. The occurrence of one or more of the events or circumstances described
in the section titled “Risk Factors,” alone or in combination with other events or circumstances, may have an adverse effect
on our business, cash flows, financial condition and results of operations. Such risks include, but are not limited to:
Risks Relating to Our Financial Position and
Capital Needs
Risks Related to our Business
● Our reliance on third parties heightens the risks faced by our business.
Risks Relating to our Intellectual Property
General Risk Factors
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PART I
Throughout this Annual Report on Form 10-K,
references to “we,” “our,” “us,” the “Company,” “Unicycive,” or “Unicycive
Therapeutics” refer to Unicycive Therapeutics, Inc.
ITEM 1. BUSINESS
Overview
We are a clinical-stage biotechnology company
focused on identifying, developing, and commercializing innovative therapies to address significant unmet medical needs, with an initial
focus on kidney disease. Founded in 2016, Unicycive was established to create a streamlined and efficient drug development platform capable
of accelerating the advancement of promising therapies from discovery to commercialization. Currently, our two programs are focused on
kidney disease, an area we believe we have the potential to offer medical benefit. Our initial focus is on developing drugs and getting
them approved in the U.S., and then to partner with global biopharmaceutical companies in the rest of the world. As we grow the company
and build our team, we intend to focus on identifying medical conditions within and outside of kidney disease. Our business model is
to license technologies and drugs in order to pursue development, regulatory approval, and commercialization of those products in global
markets. Many biotechnology companies utilize similar strategies of in-licensing and then developing and commercializing drugs. We believe,
however, that our management team’s broad network, expertise in the biopharmaceutical industry, and successful track record gives
us an advantage in identifying and bringing these assets into our company.
Our current development programs are focused
on two novel therapies: oxylanthanum carbonate, a next-generation phosphate binder for the treatment of hyperphosphatemia in chronic
kidney disease patients on dialysis, and UNI-494, a novel drug candidate in development for the treatment of acute kidney injury. oxylanthanum
carbonate and UNI-494 were initially developed by and licensed to us from Spectrum Pharmaceuticals (“Spectrum”) and Sphaera
Pharma, respectively. Spectrum conducted a Phase 1 clinical trial with oxylanthanum carbonate in 2012, prior to the grant of our license
in 2018. Sphaera conceived and performed initial characterization of various potential pro-drug linkers, including the initial patent
application. As discussed herein, after completing IND enabling preclinical studies, we have completed a Phase I clinical study in healthy
volunteers with UNI-494 in 2024.
Chronic kidney disease (CKD) is the gradual loss
of kidney (renal) function that can get worse over time leading to lasting damage and possibly Stage 5 or end-stage renal disease (ESRD).
CKD affects nearly 36 million Americans; approximately 550,000 of them have end stage renal disease and require dialysis. Hyperphosphatemia
is common in people with CKD and has been directly linked to increased morbidity and mortality for people on dialysis. For an estimated
75% of people in the U.S. on dialysis, hyperphosphatemia remains uncontrolled due to challenges with the six currently available phosphate
binders, namely insufficient potency, pill burden and unpalatable formulations. To address this significant and growing challenge, Unicycive
is developing oxylanthanum carbonate, which leverages proprietary nanoparticle technology to address the shortcomings of current therapies
by delivering higher potency that enables fewer and smaller pills — all in a formulation that is more acceptable for patients because
it is swallowed, not chewed. With OLC, if approved, people on dialysis and their physicians may have a better option to control hyperphosphatemia.
AKI is a sudden episode of kidney failure or
kidney damage (within the first 90 days of injury). After 90 days, the patient is considered to have progressed into CKD. AKI affects
more than 2 million U.S. patients and costs the healthcare system in excess of $9 billion per year. More than 300,000 patients per year
in the U.S. die due to AKI. Currently there are no FDA approved medicines to treat DGF and/or AKI. Treatment options for AKI include
continuous renal replacement therapy, renal transplant, and dialysis. In most cases the damage to the kidney is irreversible, and the
patient needs to have a renal transplant or be on dialysis for life. Therefore, there is a high unmet medical need. If approved, UNI-494
has the potential to be a first-in-class drug for the treatment of AKI.
We operate with a sense of urgency to bring new
treatments to patients faster, leveraging our team’s expertise, operational efficiency, and strategic focus on high-value opportunities
within the renal space. Through this approach, we aim to deliver innovative therapies that provide meaningful clinical and economic benefits
for patients, providers, and healthcare systems.
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Pipeline
Our proprietary pipeline is comprised of our two product candidates
– oxylanthanum carbonate and UNI-494 – which are described below in Figure 1:
Figure 1: Unicycive Therapeutics’ Pipeline
Oxylanthanum Carbonate
Oxylanthanum carbonate (lanthanum dioxycarbonate)
is an investigational next-generation lanthanum-based phosphate binding agent being developed for the treatment of hyperphosphatemia
in CKD patients on dialysis.
Oxylanthanum carbonate is a phosphate binder
for the treatment of hyperphosphatemia in patients with CKD on dialysis and is intended to be administered as a tablet that will be swallowed
whole at mealtimes. CKD patients typically have co-morbidities, which often require them to be on strict pill schedules. Current phosphate
binder products involve patients needing to take a large number of pills daily, some of which are large and/or must be chewed, often
resulting in poor adherence to the prescribed drug therapy.
By virtue of its novel nanoparticle technology,
OLC leverages the high phosphate binding potency of lanthanum in a palatable dose form that has the potential to substantially reduce
the pill burden volume for patients. In this regard, we believe that the combined effect of smaller pill size, lower number of pills,
and improved palatability with Oxylanthanum carbonate will compete favorably with currently available phosphate binders and may lead
to improved patient compliance/adherence and more effective disease management.
We are seeking the U.S. Food and Drug Administration
(FDA) approval of OLC via the 505(b)(2) regulatory pathway. In September 2024, we submitted a New Drug Application (NDA) for
OLC to the FDA. In November 2024 we announced the FDA had accepted its NDA and set a Prescription Drug User Fee Act (PDUFA) target
action date of June 28, 2025. In June 2025, the FDA issued us a Complete Response Letter (CRL) notifying us that a third-party
manufacturing vendor of its main contract development and manufacturing organization (CDMO) was cited for deficiencies following a cGMP
inspection. No other concerns have been identified to us, including pre-clinical, clinical, or safety data submitted as part
of the NDA. In October 2025, we held a Type A meeting with the FDA to discuss the resolution of the single deficiency identified
in the CRL related to the compliance status of a third-party manufacturing vendor. Following receipt of the official meeting minutes
from the Type A meeting and engaging in discussions with its third-party manufacturing vendor, we resubmitted its NDA to the FDA
in December 2025. In January 2026, the FDA accepted the resubmission of the NDA for OLC, deeming the resubmission to be a Class II complete
response which has a six-month review period from the date of resubmission, and set a PDUFA) target action date of June 29, 2026.
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Disease Overview: Hyperphosphatemia
Chronic kidney disease (CKD) is the gradual loss
of kidney (renal) function that can get worse over time leading to lasting damage and possibly Stage 5 or end-stage renal disease (ESRD).
The stages of chronic kidney disease are shown below in Figure 2.
eGFR = estimated glomerular filtration rate (a measure of kidney
function)
Image Source: https://www.kidney.org/kidney-topics/stages-chronic-kidney-disease-ckd
Figure 2: Stages of Chronic Kidney
Disease
According to the United States Renal Data System
(USRDS) 2022 Annual Data Report, 30 million (14%) of adults in the United States are estimated to have CKD and, of these, approximately
13 million patients have advanced CKD (stage 3-5). Complications of CKD include electrolyte imbalances, fluid build-up, anemia, bone
disease, and heart disease. Most patients with Stage 5 CKD (ESRD) either undergo kidney transplantations or go on dialysis. The 2023
USRDS annual report indicates that there were 541,326 prevalent dialysis patients in 2021 (the latest reported year), and of those, approximately
450,000 patients (~80%) take phosphate binders to control hyperphosphatemia. The prevalent U.S. dialysis population has grown at an average
yearly rate of 3.5% over the past decade. The number of patients with ESRD in the U.S. is increasing steadily and is projected to reach
between 971,000 and 1,259,000 patients in 2030.
Hyperphosphatemia is a bone and mineral metabolism
disorder in which elevated phosphorus levels in the blood lead to cardiovascular complications and vascular calcification (hardening).
According to Kidney Disease Improving Global Outcomes (KDIGO) guidelines, hyperphosphatemia is defined as an abnormally high serum phosphorus
concentration >4.5 mg/dL. In CKD, hyperphosphatemia is caused by a chronic dysregulation of serum phosphorus levels as a result of
progressive kidney damage. In healthy people, normal serum phosphorus levels are maintained in the body by the absorption from food and
subsequent excretion from the body via urine and feces. In people with CKD, not enough phosphate is excreted, leading to elevated levels
of phosphorus in the blood.
According to a 2009 paper authored by Covic,
hyperphosphatemia is associated with increased risk of cardiovascular disease, metabolic bone disease, and deaths from all-causes (all-cause
mortality). According to a study completed by Palmer in 2011, it is estimated that all-cause mortality is increased by 18% for every
1 mg/dL increase in serum phosphorus concentration.
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Current Treatment of Hyperphosphatemia
The treatment goal for patients with hyperphosphatemia
is focused on controlling the level of phosphate in the body. KDIGO guidelines recommend three main strategies for managing hyperphosphatemia:
dietary intake restrictions, use of phosphate binders, and dialysis, as shown in Figure 3 below.
Figure 3: KDIGO Guidelines Recommend Three
Main Strategies for Managing Hyperphosphatemia
While KDIGO guidelines do not recommend one phosphate
binder over another, they do recommend restricting the dose of calcium-based binders and avoiding long-term use of aluminum-containing
binders. This means that physicians prescribe their medication of choice, usually based on clinical factors and patient preferences.
Utilization of calcium-based binders is discouraged by the most recent KDOQI/KDIGO guidelines due to mounting clinical evidence that
excess calcium load from calcium-based phosphate binder is associated with hypercalcemia and cardiovascular calcification which has been
associated with an increased risk of morbidity (disease) and mortality (death).
According to data from the Dialysis Outcomes
and Practice Patterns Study (DOPPS) in 2021, 82% of U.S. dialysis patients were prescribed phosphate binders, which equates to approximately
450,000 patients.
Unmet Medical Need in the Management of Hyperphosphatemia
The brief descriptions of the mechanism of action
and what we believe to be the advantages and disadvantages of various phosphate binders are shown below in Figure 4.
Figure 4: Phosphate Binder Mechanisms
of Action, Adapted from Covic and Rastogi, 2013.
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Despite the commercial availability of the six
phosphate binders in the table above, 75% of U.S. dialysis patients fail to achieve the serum phosphorus target levels established by
the KDIGO guidelines. Moreover, the percentage of patients achieving these serum phosphorus guidelines is trending downward — underscoring
the need for new and effective treatment options (Figure 5).
KDOQI: The Kidney Disease Outcomes Quality Initiative
Figure 5: Serum Phosphorus Target Achievement from 2012 to 2021
In 2005, Unruh, ML published a paper that showed poor adherence
to treatment is common in patients with ESRD and has been associated with an increased risk of mortality. In addition, poor adherence
to phosphate binder therapy has been associated with failure to adequately control serum phosphorus concentrations as shown in a publication
by Arenas, MD and others in 2010. Results from a study of 233 patients on maintenance dialysis from three different dialysis units in
the U.S. showed that patients took a mean of 11 ± 4 medications with a median daily pill intake of 19 as shown by Chiu, YW in
2009. Phosphate binders accounted for nearly 50% of the total pill burden, with a median daily pill count of nine. Only 38% of patients
in this study reported that they were adherent to their prescribed phosphate binder therapy and adherence decreased significantly with
increased pill count.
Potential strategies to improve adherence to
phosphate binders in patients with ESRD include: (i) a reduction in pill size and number, (ii) improvement of palatability, and (iii)
a reduction in associated adverse effects as published in a study by Covic and Rastogi in 2013.
Therefore, we believe there is a current need
for better phosphate binders with high phosphate binding capacity, enabling a reduced pill burden for better medication compliance.
By virtue of its novel nanoparticle technology,
OLC leverages the high phosphate binding potency of lanthanum in a palatable dose form that has the potential to substantially reduce
the pill burden volume for patients. In this regard, we believe that the combined effect of smaller pill size, lower number of pills,
and improved palatability with oxylanthanum carbonate compared with currently available phosphate binders may lead to improved patient
compliance/adherence and more effective disease management.
-5-
Development of Oxylanthanum Carbonate
Oxylanthanum Carbonate Mechanism of Action
Oxylanthanum carbonate binds to phosphates and
forms an insoluble lanthanum phosphate complex which is then excreted via the feces. This results in reduced absorption of phosphate
leading to a reduction of serum phosphorus levels.
In rat studies, oxylanthanum carbonate exhibited
comparable reduction in the urine phosphorus excretion following administration of a lower dose of drug product (0.40g) vs a higher dose
(0.57g) of Fosrenol® (lanthanum carbonate tetrahydrate) which is a currently approved lanthanum-based phosphate binder. While differing
in the mass of drug product, each dose contained comparable amounts of the active moiety (elemental lanthanum). In the same study, at
equivalent doses, Oxylanthanum carbonate was superior to Sevelamer (the most commonly used phosphate binder) in reducing urine phosphorus
excretion (see Figure 6 below).
Figure 6: Urine Phosphate Levels in Rats Following
Comparable Dosing of Oxylanthanum Carbonate, Fosrenol, or Sevelamer
In animal toxicology studies with oxylanthanum
carbonate no unexpected toxicity was found and systemic absorption of lanthanum was extremely low, which is consistent with similar studies
conducted with Fosrenol.
The chemical structure of oxylanthanum carbonate
was designed to allow for a smaller tablet size and require fewer pills compared with currently available phosphate binder alternatives,
specifically with a dosing regimen of only one tablet per meal. The oxylanthanum carbonate tablet is designed to disintegrate rapidly
in the stomach after swallowing and does not need to be chewed.
Clinical Trial Experience
Unicycive is seeking FDA approval of OLC via
the 505(b)(2) regulatory pathway. The NDA submission package is based on data from three clinical studies: a first in human Phase I study
in healthy volunteers, a Bioequivalence (BE) study in healthy volunteers, and a pivotal Phase 2 tolerability study of OLC in CKD patients
on dialysis, as well as multiple preclinical studies, and the chemistry, manufacturing and controls (CMC) data.
Pivotal Phase 2 Study
We conducted a Phase 2, open-label, single-arm,
multicenter trial in adult patients receiving maintenance hemodialysis with hyperphosphatemia. The primary objective was to evaluate
the tolerability of OLC at clinically effective doses with a goal serum phosphate concentration (sP) ≤5.5 mg/dL. The trial included
washout, titration, and maintenance periods. Eligible patients had sP ≥4.0 and ≤7.5 mg/dL for at least 8 weeks prior to screening
while receiving thrice weekly hemodialysis and a stable phosphate binder regimen. Patients started titration when sP was >5.5 mg/dL
and entered maintenance once sP was ≤5.5 mg/dL. The starting dose of OLC during titration was 1500 mg/day (500 mg thrice daily).
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In the study, 106 patients were enrolled, of
which 86 patients entered titration and were followed as the Safety Population. Of the 86, 78 entered the maintenance period. Of the
78 patients that entered maintenance, 7 patients did not have phosphate control, leaving an Evaluable Population of 71 patients, exceeding
the planned enrollment number of 60. Of the 86 patients, the trial enrolled 47 males and 39 females with a mean age of 62. Renvela®
was the most prescribed phosphate binder for patients entering the study.
Primary Endpoint - Tolerability: The objective
of the OLC-201 trial was to evaluate the tolerability of clinically effective doses of OLC in CKD patients on dialysis. A clinically
effective dose was established when a patient achieved a serum phosphate level ≤5.5 mg/dL. Tolerability was assessed based on the
incidence of treatment-related AEs leading to discontinuation from the study in the maintenance period. In the OLC-201 trial, there was
only 1 discontinuation due to a treatment-related AE in the Evaluable Population, a rate of 1.4%. In the Safety Population of 86 patients
there were only 3 treatment-related discontinuations, a rate of 3.5%. In total, 5 patients discontinued due to AEs in the Safety Population,
3 were related to OLC and 2 were deemed unrelated to OLC.
Secondary Endpoint - Safety: The secondary
endpoint assessing safety was reported as the treatment-related AEs occurring in ≥5% of patients. The safety analysis covered all
86 patients in the Safety Population. Consistent with the AEs observed with other phosphate binders, the AEs were gastrointestinal related
with diarrhea and vomiting being the most common at 9% and 6% respectively. There were no treatment-related serious adverse events (SAEs).
Six patients experienced SAEs but those were deemed not related to OLC treatment. Most treatment-related AEs were mild to moderate in
severity with only 2 AEs reported as severe. (Figure 7)
Figure 7: OLC Pivotal Phase 2 Trial Treatment-Related
Adverse Events
Serum Phosphate Control: While the UNI-OLC-201
study was not designed to evaluate efficacy, the trial enrolled patients on stable doses of approved hyperphosphatemia medications. At
baseline 59% of patients had phosphate levels ≤5.5 mg/dL, the level recommended by KDOQI guidelines. After washout from the prior
phosphate binders, 90% of patients were able to achieve phosphate levels ≤5.5ng/dL at the end of titration with OLC. This includes
the last serum phosphate levels from all patients including those that discontinued during titration: 77/86 (90%) (Figure 8).
In addition, 69% of the 71 Evaluable Patients achieved a target serum phosphate level of ≤5.5 mg/dL at OLC doses of 1500 mg/day or
lower. (Figure 9)
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Figure 8: 90% Of Patients Were Able to Achieve
Phosphate Levels ≤5.5ng/dL with OLC.
Figure 9: 69% of the 71 Evaluable Patients
Achieved a Target Serum Phosphate Level of ≤5.5 mg/dL at OLC Doses of 1500 mg/Day or Lower
First-in-Human Phase 1 Study
In September 2012 a Phase 1 single-center clinical
trial evaluating oxylanthanum carbonate in 32 healthy volunteers was completed in the United States. Four sequential dose cohorts of
8 subjects each (6 actives and 2 placebos) received oxylanthanum carbonate at 1500, 3000, 4500, or 6000 mg/day, taken orally in 3 divided
doses within 15 minutes after meals, for five consecutive days. The primary endpoint of the study was the evaluation of safety, and the
secondary endpoint was the phosphate binding capacity of oxylanthanum carbonate as judged by the level of phosphorus in feces and urine.
We believe the study indicated that oxylanthanum carbonate was minimally absorbed to the systemic circulation and was well-tolerated
at doses up to 6000 mg/day. oxylanthanum carbonate significantly reduced urine phosphate excretion and significantly increased fecal
phosphate excretion at doses at and above 3000 mg/day. The mean overall change in phosphorus from baseline in both urine and feces,
across all treatment groups, showed a dose-response trend that was statistically significant (p<0.0001 and p=0.0004, respectively).
The mean reduction in urine phosphorus excretion was not significant at 1500 mg/day (p=0.3676) but was significant at 3000 (p=0.0004),
4500 (p<0.0001), and 6000 (p=0.0001) mg/day, as shown in the figure below.
The mean reduction in urine phosphorus excretion
was significant (p<0.001) at all four doses of oxylanthanum carbonate (Figure 10).
Figure 10: Daily Urine Phosphate Reduction in Healthy Volunteers
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Oxylanthanum Carbonate Bioequivalence Study
in Healthy Volunteers
We conducted a randomized,
open label, two-way crossover bioequivalence BE study to establish the bioequivalence of the phosphate binding capacity of oxylanthanum
carbonate and Fosrenol. The primary objective of the study was to demonstrate PD equivalence of orally administered oxylanthanum carbonate
1000 mg three-times daily (TID) to orally administered Fosrenol 1000 mg TID in healthy subjects, and the secondary objective was to compare
the safety and tolerability of oxylanthanum carbonate versus Fosrenol in healthy subjects. The study design, including the dose, primary
endpoint and the sample size was reviewed by the Agency prior to the initiation of the study. The primary outcome measure was least squares
(LS) mean change in urinary phosphorous excretion (in mg/day) from baseline to the evaluation period. The evaluation period was defined
as the approximately 72-hour urine collection period starting on Day 1 and ending on Day 4. Baseline was defined as the approximately
48-hour urine collection period starting on Day -2 and ending on Day 1. PD equivalence was to be claimed if the 90% confidence interval
(CI) of the primary PD variable for oxylanthanum carbonate was completely contained within the reference interval, which was defined
as ±20% of the LS mean of the primary PD variable for lanthanum carbonate. The LS mean change from Baseline for oxylanthanum carbonate
(-320.4 mg/day) was similar to the LS mean change from Baseline for Fosrenol (-324.0 mg/day). The 90% CI for the LS mean was (-37.83,
45.12), which is well within the acceptance range of (-64.80, 64,80). It was concluded that oxylanthanum carbonate was bioequivalent
to Fosrenol. Primary outcome data is presented in the table below (Figure 11).
Figure 11: Summary of Mean Change in
Urinary Phosphorus Excretion (mg/day)
Regulatory Guidance
We are seeking
approval for oxylanthanum carbonate from the U.S. Food and Drug Administration (FDA) through the 505(b)(2) regulatory pathway. The
505(b)(2) pathway allows for full approval of a drug using data from an approved drug with the same active moiety. The approved drug
is called the Reference Listed Drug (RLD). The RLD for the oxylanthanum carbonate submission is Fosrenol (lanthanum carbonate). The
FDA recommended conducting a BE study in healthy volunteers and a 6-month toxicity study in mice with both oxylanthanum carbonate
and Fosrenol to be able to rely on the efficacy and safety of Fosrenol. We completed both studies and submitted the data for the
FDA’s review during the pre-NDA (New Drug Application) meeting request. After reviewing the data, the Agency recommended that
we conduct a tolerability study of oxylanthanum carbonate in chronic kidney disease patients on dialysis before filing the NDA. We
gained alignment with the FDA on the study design, sample size, and endpoints of the proposed pivotal clinical study during a Type-C
meeting in September 2023. This study was initiated in December 2023 and reported positive results in June 2024. We announced the
OLC NDA submission in September 2024 and received a PDUFA date of June 28, 2025. In June 2025 the FDA issued us a Complete Response
Letter (CRL) notifying us that a third-party manufacturing vendor of its main contract development and manufacturing organization
(CDMO) was cited for deficiencies following a cGMP inspection. No other concerns have been identified to the Company, including
pre-clinical, clinical, or safety data submitted as part of the NDA. In October 2025 we held a Type A meeting with the
FDA to discuss the resolution of the single deficiency identified in the CRL related to the compliance status of a third-party
manufacturing vendor. Following receipt of the official meeting minutes from the Type A meeting and engaging in discussions with its
third-party manufacturing vendor, we resubmitted its NDA to the FDA in December 2025. In January 2026, the FDA accepted the
resubmission of the NDA for OLC, deeming the resubmission to be a Class II complete response which has a six-month review period
from the date of resubmission, and set a PDUFA) target action date of June 29, 2026.
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U.S. Commercial Opportunity for Oxylanthanum
Carbonate
Overview
Unicycive Therapeutics is a biopharmaceutical company dedicated to
developing and commercializing innovative therapies for patients with kidney disease. Our lead product candidate, oxylanthanum carbonate
(OLC), is a next-generation, orally administered, non-calcium-based phosphate binder being developed for the treatment of hyperphosphatemia
in patients with chronic kidney disease (CKD) on dialysis.
We are transitioning from a clinical-stage organization to a commercial-stage
company in anticipation of the potential U.S. approval and launch of OLC. Our strategy is to establish OLC as a differentiated therapy
within the hyperphosphatemia treatment paradigm while building a focused nephrology franchise supported by disciplined commercial execution
and capital-efficient infrastructure.
Our commercial organization is led by executives with significant
expertise in nephrology and dialysis markets. Members of our leadership team have extensive experience launching and managing renal franchises,
including navigating the Medicare End-Stage Renal Disease (ESRD) Prospective Payment System (PPS), contracting with dialysis organizations,
and executing within highly concentrated provider environments.
Our objective is to combine a differentiated clinical profile, a concentrated
go-to-market model, and a strategically aligned reimbursement approach to support meaningful adoption of OLC.
Commercial Strategy: Oxylanthanum Carbonate
(OLC)
U.S. Market Opportunity and Unmet Need
Hyperphosphatemia is a near-universal complication
among the approximately 550,000 dialysis patients in the United States. Elevated serum phosphorus levels are associated with secondary
hyperparathyroidism, renal bone disease, vascular calcification, and increased cardiovascular morbidity and mortality. Effective phosphate
management is therefore a foundational component of dialysis care.
Approximately 80% of dialysis patients are prescribed
phosphate-lowering therapies (PLTs), representing a total addressable U.S. market of more than 440,000 patients. The global market for
hyperphosphatemia therapies is estimated to be approximately $2.5 billion annually, with the U.S. market accounting for more than $1
billion.
Despite multiple available therapeutic options,
significant unmet need persists:
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Because dialysis patients require chronic, lifelong
phosphate management, therapies that improve ease of administration and reduce pill burden may have important clinical and economic implications.
Our Solution: Oxylanthanum Carbonate (OLC)
OLC is designed to address limitations of current phosphate binders
through a proprietary formulation intended to combine potency with reduced medication volume.
We believe OLC offers the following potential advantages:
By directly addressing pill burden and administration
challenges, OLC is intended to improve patient experience and potentially support adherence within this chronic treatment population.
Commercial Readiness and Organizational Development
Leadership and Talent
We have recruited a commercial leadership team
with deep nephrology experience, including prior hyperphosphatemia launches and dialysis organization contracting expertise. Our embedded
commercial team includes Marketing, Market Access, Medical Affairs, Professional Relations, and Commercial Operations functions.
These teams maintain established relationships
with key opinion leaders (KOLs), high-volume prescribers, and dialysis organization decision-makers.
Market Development Activities
During OLC pre-launch market development, our teams have:
● Participated in major nephrology conferences
● Published and presented OLC-related clinical data
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Commercial Operations Infrastructure
Throughout 2025 and early 2026, we have significantly
accelerated our commercial readiness activities to support the pending U.S. approval and launch of OLC. We have evolved from a development-led
organization into a launch-ready commercial enterprise by establishing the relevant infrastructure and systems to support our commercial
teams.
● Advanced CRM systems
● Data analytics platforms for physician segmentation
● Compliance frameworks and internal controls
● Medical information and pharmacovigilance systems
● Scalable supply chain and logistics infrastructure
Targeted Sales and Account Management
Our market analysis indicates that the U.S. nephrology market is highly
concentrated. While there are more than 10,000 total prescribers of phosphate lowering therapies (PLTs), our data shows that the approximately
2,100 highest prescribers are responsible for half of the prescriptions written for PLTs annually.
Dialysis Market Concentration
The U.S. dialysis market is highly consolidated. A limited number
of dialysis organizations treat the substantial majority of the approximately 550,000 U.S. dialysis patients.
U.S. Renal Care (including Satellite-administered network) ~37,000 ~78%
Dialysis Clinic, Inc. (DCI) ~15,000 ~81%
The source is: The National Forum of ESRD Networks. Quarterly National
ESRD Census www.esrdnetworks.org
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Collectively, these organizations influence treatment decisions for
approximately 85% of U.S. dialysis patients through centralized medical leadership, formulary governance, group purchasing organizations,
and aligned specialty pharmacy networks.
Because oral-only phosphate binders are reimbursed within the ESRD
PPS bundled payment for Medicare beneficiaries, dialysis organizations play a meaningful role in therapy adoption decisions. Successful
contracting, formulary positioning, and clinical protocol integration within a limited number of dialysis organizations may therefore
provide access to a substantial majority of bundled Medicare dialysis patients.
This concentrated structure enables a focused and capital-efficient
commercial strategy centered on high-volume prescribers and key dialysis accounts.
Distribution and Logistics
We have established a streamlined and capital-efficient distribution
model designed to support broad and reliable access to OLC shortly following FDA approval.
Market Access and Reimbursement Strategy
Phosphate Lowering Therapies (PLTs) Payer
Mix
Phosphate-lowering therapies are reimbursed through two primary pathways:
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Supporting OLC Market Access for Non-Medicare
Patients
We intend to establish UniSourceTM, a comprehensive reimbursement
support program designed to facilitate access for patients covered under commercial and Medicaid plans. UniSourceTM will provide
the following high-touch, friction-minimizing reimbursement support to providers and patients:
● Benefit investigations
● Prior authorization and appeals support
● Co-pay assistance programs for eligible commercially insured patients
● Patient assistance programs for uninsured or underinsured patients
Navigating the Bundled Medicare Reimbursement
Environment
Over two thirds of our target patient population
is covered by Medicare. Effective January 1, 2025, CMS transitioned oral-only phosphate binders into the ESRD PPS bundled payment. To
promote innovation within the bundle, CMS provides the Transitional Drug Add-on Payment Adjustment (TDAPA). If OLC receives FDA approval,
we intend to apply for TDAPA.
If granted, TDAPA would provide separate reimbursement
for OLC at 100% of Average Sales Price (ASP), for a two-year period.
Following the initial 2-year TDAPA period, CMS
has established a transitional risk-sharing adjustment under which dialysis organizations may receive an additional payment equal to
65% of incremental costs above the bundled rate during a defined transition period of 3 years.
The TDAPA period applicable to certain existing
phosphate binders is expected to conclude at the end of 2026, after which CMS is expected to incorporate related expenditures into a
rebased ESRD PPS bundled rate. If OLC receives approval and is granted TDAPA with an anticipated first-half 2027 launch, OLC may be the
only phosphate binder eligible for separate reimbursement during its TDAPA period. In such a scenario, dialysis organizations could receive
both rebased bundle payments reflecting prior phosphate binder utilization and separate reimbursement for OLC during its separate TDAPA
period. We believe this dynamic may create a favorable economic framework for rapid evaluation and adoption of OLC.
Congressional legislation currently under consideration,
the Kidney Care Access Protection Act (KCAPA), proposes potential enhancements to TDAPA duration (from 2 to 3 years) and post-TDAPA payments
(from 3 years to perpetuity) which may substantially expand the revenue potential for OLC. We cannot predict whether such legislation
will be enacted.
Competition
The market for hyperphosphatemia treatments is
highly competitive and characterized by a well-established standard of care. Our potential competitors include biopharmaceutical innovators
and generic companies that market calcium-based binders, non-calcium-based binders, and novel phosphate absorption inhibitors.
Current Landscape and Limitations of Standard
of Care
Existing therapies are often limited by significant
patient hurdles, primarily high pill burden and poor gastrointestinal (GI) tolerability. Standard-of-care binders, such as sevelamer
carbonate, often require patients to ingest up to 10–12 large tablets daily. This “pill fatigue” contributes to low adherence,
with studies suggesting a significant portion of dialysis patients fail to achieve target phosphorus levels.
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Primary Competitors
Category Leading Products OLC Competitive Advantage
Figure 12: Primary competitors of OLC
Our Competitive Advantage: Oxylanthanum Carbonate
(OLC)
We believe OLC is positioned to disrupt the current
treatment paradigm through its proprietary formulation, which offers:
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Global Strategy and Strategic Partnerships
We retain full global commercial rights to OLC,
except in certain territories where we have established strategic licensing partnerships.
In Greater China, we have licensed rights to
Lee’s Pharmaceutical Holdings Limited, which is responsible for regulatory approval and commercialization within the territory.
In select Asian markets, we have entered into a licensing agreement with Lotus Pharmaceutical Co., Ltd., which is responsible for regulatory
filings, commercialization, and distribution within its designated regions. Under these agreements, we are eligible to receive milestone
payments and tiered royalties on net sales.
These partnerships allow us to leverage established
regional infrastructure while preserving capital and maintaining strategic focus on the U.S. market.
While our primary near-term focus is a self-directed
U.S. launch of OLC, we continue to evaluate complementary strategies, including potential co-promotion or distribution partnerships,
where such arrangements may enhance market penetration and long-term franchise value.
Strategic Vision
We view OLC as the foundation of a focused nephrology
franchise. By leveraging our dialysis relationships, reimbursement expertise, and commercial infrastructure, we aim to establish a durable
presence in the renal therapeutic landscape and evaluate additional complementary opportunities over time
Manufacturing
We do not own or operate manufacturing facilities
for the production of clinical or commercial quantities of our product candidates. We currently have no plans to build our own clinical
or commercial scale manufacturing capabilities. If and when any of our product candidates are approved, we plan to obtain manufacturing
capacity through contract manufacturing organizations (CMOs) to meet projected needs for commercial sale quantities and serve patient
needs.
With regards to manufacturing, testing and potential commercial supply
of oxylanthanum carbonate, on October 31, 2020, the Company entered into an agreement with Shilpa Medicare Ltd (“Shilpa”)
based in India. Pursuant to the Agreement, Shilpa provides certain development, manufacturing, supply and other CMC-related services related
to the development and commercialization of oxylanthanum carbonate (“OLC”).
In June 2024, we entered into the First Amendment
to Manufacturing and Supply Agreement with Shilpa (the “Amendment”) in anticipation of an increased manufacturing demand
for OLC. Pursuant to the Amendment, we agreed to make a binding purchase order for tablets of OLC and Shilpa has agreed to deliver such
order by September 30, 2025. In addition, we agreed to order additional tablets for delivery between December 31, 2025, and September
30, 2026. Further, we agreed to make certain milestone payments and to provide certain funding to Shilpa for a new manufacturing line.
The initial term of the Agreement shall continue until the eighth (8th) anniversary of the date of receipt by us of FDA approval of our
NDA of OLC (the “Initial Term”). Following the Initial Term, the Agreement shall continue in effect for consecutive periods
of four (4) years each unless earlier terminated pursuant to the terms of the Agreement.
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Oxylanthanum Carbonate Purchase Agreement
On September 20, 2018, we entered into an Assignment
and Asset Purchase Agreement (the “Spectrum Agreement”) with Spectrum Pharmaceuticals, Inc. (“Spectrum”), pursuant
to which we purchased certain assets from Spectrum, including Spectrum’s right, title, interest in and intellectual property related
to oxylanthanum carbonate RZB 012, also known as RENALANTM (“Renalan”) and RZB 014, also known as SPI 014 (“SPI”