Unicycive Therapeutics, Inc.

Unicycive Therapeutics is a different type of biotech company. Unlike most firms in this space, Unicycive was built from the ground up in only three years. Additionally, they are focused on diseases of the kidney, a space that has had a shortage of effective and convenient solutions.

Chronic Kidney Disease (CKD) ranges between stages 1 through 5, with 1 being the least severe and 5 being the most. Stage 5 is called End-Stage Renal Disease (ESRD), where kidney function has declined to the point that patients require a kidney transplant or go on long-term dialysis to maintain life. At this late stage of CKD, elevated phosphorus,  known as hyperphosphatemia, becomes a serious problem that needs to be addressed. Unfortunately, phosphate control can become a real challenge for CKD patients because, currently, available therapies require a burdensome number of large pills.  Unicycive's drug Oxylanthanum Carbonate (OLC), if approved, promises to reduce that burden dramatically. 

That phosphate control can become incredibly uncomfortable for ESRD sufferers as the number of pills that are necessary can be a major burden. Unicycive's drug Oxylanthanum Carbonate (OLC) intends to reduce that burden dramatically.

Unicycive's management team and board of directors are steeped in experience, both in the medical industry as well as with drug commercialization. Additionally, their scientific board holds the impressive levels of experience and knowledge necessary to properly guide the firm and solve its most pressing issues.

Source: Company Documents

OLC may reduce pill burden volume by more than 4-fold, compared to the most prescribed phospate binder.

Source: Company Documents

For any biotech company looking to build a pipeline and create the next important pharmaceutical, having strong financing in place is critical. You need a sufficient runway to see a pharmaceutical solution from concept through the regulatory process and into the market.

Unicycive recently announced in March 2024 a $50 million private placement, providing significant funding to support its clinical development pipeline. The financing, led by new investors Octagon Capital and Great Point Partners, LLC, with participation from other institutional investors, ensures that Unicycive can advance its lead drug, Oxylanthanum Carbonate (OLC), through the approval process and prepare for a commercial launch.

In addition to this $50 million, Unicycive has access to up to $100 million in committed capital through future warrant exercises. The warrants are linked to significant milestones in the regulatory process, with Tranche A warrants exercisable upon FDA approval for OLC, Tranche B exercisable upon TDAPA approval, and Tranche C exercisable after four quarters of commercial sales. This additional funding commitment underscores the investors' confidence in Unicycive's programs and their potential for success.

Proceeds from the private placement will also support Unicycive's NDA submission with the FDA for approval of OLC for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis. This funding positions Unicycive to navigate regulatory hurdles and successfully bring its innovative treatments to market.

With this robust financial backing, Unicycive is well-equipped to advance both its lead program, OLC, and its secondary program, UNI-494, focused on acute kidney injury, toward clinical and commercial success.

Source: Company Documents

Unicycive's Single-Minded Attention:

Focused on developing new treatment options for renal diseases.

Source: Company Documents

Treating End-Stage Renal Disease (ESRD) demands effective phosphate control to avoid complications such as heart failure. Current solutions often require burdensome and expensive regimens with large pills. Oxylanthanum Carbonate (OLC) is positioning itself as a novel and elegant solution to this problem.

OLC is an advanced phosphate-binding agent using proprietary nanoparticle technology, designed to treat hyperphosphatemia in chronic kidney disease (CKD) patients on dialysis. The nanoparticle technology increases the surface area of active drugs, allowing more medicine in smaller pills that can be swallowed whole, reducing the pill burden.

Unicycive Therapeutics completed a clinical trial with 32 healthy volunteers to study OLC. This study showed that OLC was minimally absorbed into the systemic circulation and was safe and well-tolerated at doses up to 6000 mg/day. The results indicated that OLC significantly reduced urine phosphate excretion and increased fecal phosphate excretion at doses at and above 3000 mg/day, demonstrating its potential effectiveness in managing hyperphosphatemia.

OLC* is a novel investigational phosphate binder for the treatment of hyperphosphatemia in patients with chronic kidney disease on dialysis. Its mechanism of action involves binding to dietary phosphate in the gastrointestinal tract, which is then excreted via the feces, leading to a reduction in serum phosphorus levels. The key features of OLC include:

• Enhanced surface area due to nanoparticle technology

• Lower molecular weight

• Immediate-release tablets

• Smaller pills

• Swallowed whole (not chewed)

*OLC is an unapproved investigational new drug being developed under the FDA's 505(b)(2) regulatory procedure. If approved, it will share the same product label and prescribing information as the reference-listed drug Fosrenol (lanthanum carbonate), with the advantage of smaller pills that can be swallowed whole with water, not chewed.

Unicycive has a strong patent portfolio protecting OLC, with a family of U.S. patents and corresponding patents in Canada, Europe, Japan, China, Australia, and other countries.

Both the U.S. and foreign patents were filed in 2011, with a statutory expiration in 2031. This patent protection offers Unicycive the potential to deliver significant shareholder value for years to come.

Unicycive believes mitochondria play a critical role in Acute Kidney Injury (AKI) due to their dual role as the primary source of cellular energy and key regulators of cell death. Mitochondrial damage in AKI can lead to sublethal and lethal injury of kidney tubules, resulting in a loss of renal function.

Disruption in mitochondrial dynamics and compromised membrane integrity can trigger the release of apoptogenic factors, mitochondrial permeability transition (MPT) pores, loss of membrane potential, energetic failure, and reactive oxygen species production, leading to cell injury and death.

Currently, there are no FDA-approved medicines to treat AKI. Damage to the kidney is often irreversible, requiring renal transplant or lifelong dialysis.

UNI-494 is a novel chemical entity targeting mitochondrial dysfunction, with the potential to address AKI's unmet medical needs. UNI-494 is in preclinical development for the treatment of AKI, derived from a marketed agent, nicorandil, and designed to improve mitochondrial function by blocking the opening of MPTP pores in the inner mitochondrial membrane.

1. UNI-494 is a prodrug of nicorandil with improved properties and an extended patent life.

2. Nicorandil has compelling scientific data supporting the development of UNI-494 for Acute Kidney Disease (AKI) and Chronic Kidney Disease (CKD).

3. Unicycive is focusing on AKI as the initial indication, with CKD as a possible follow-on program.

Unicycive Therapeutics is executing its go-to-market strategy for UNI-494, aiming to advance the drug through preclinical studies and regulatory filing to initiate clinical trials. The company has achieved key milestones, including completing preclinical studies, manufacturing drug supplies for clinical studies, and obtaining MHRA approval to initiate the first human trial. The Phase 1 clinical trial was initiated in Q1 2023, and Unicycive is working toward an FDA IND filing for a Phase 2 proof-of-concept study.

FDA Regulatory Strategy:

• Confirm prodrug tolerability in animal studies at desired doses.

• Identify prodrug dose(s) for initial human study and demonstrate conversion of UNI-494 to nicorandil in humans.

• Seek regulatory clearance to initiate Phase 1 study.

Unique attributes for regulatory approval of UNI-494:

• Leverage preclinical and clinical data from nicorandil outside the United States with a comparability package.

• Design a more homogenous AKI patient population, including patients with contrast-induced nephropathy (CIN), where nicorandil has been shown to be efficacious.

Milestones

Animal safety studies completed

Drug supplies for clinical studies manufactured

MHRA approval to initiate first-in-human trial

Phase 1 initiated (Q1 '23)

Ongoing regulatory filing process to support the Phase 2 proof-of-concept (POC) study

Chronic Kidney Disease is a very significant issue across much of the world. According to Research and Markets, the global end stage renal disease (ESRD) market size is anticipated to reach over $260 billion by 2030, leading to a very robust Compound Annual Growth Rate (CAGR) of 12.9% from 2022 to 2030. An increasing number of patients suffering from kidney failure, the rapid increase in the volume of hospitals & urgent care centers, and growing hospital admission rates are thought to be the catalysts behind this growth. Both of the company's programs have the potential to participate in this market.

Unicycive Therapeutics' lead program, Oxylanthanum Carbonate (OLC), is designed to address hyperphosphatemia, a condition characterized by elevated phosphate levels in patients with chronic kidney disease undergoing dialysis. The global hyperphosphatemia treatment market was estimated to be $2.5 billion in 2021. With a projected Compound Annual Growth Rate (CAGR) of 5.3% between 2021 and 2028, the current market may be close to $3.0 billion, highlighting a significant opportunity for Unicycive's OLC.

Go-to-Market Strategy and Partnerships:

Unicycive's go-to-market strategy involves strategic partnerships to expand the reach and accelerate the commercialization of Oxylanthanum Carbonate. In Q4 2022, Unicycive entered an agreement with Lee's Pharmaceutical (HK) Limited, granting exclusive rights to develop, market, and commercialize OLC in Mainland China, Hong Kong, and certain Asian markets. This agreement provides Unicycive with a strong local partner with deep domain expertise, unlocking significant growth potential in one of the largest markets for kidney disease patients.

As part of the agreement, Unicycive received an upfront payment of $1.0 million and is eligible for royalties on sales and other milestone payments. This strategic partnership enhances Unicycive's presence in Asia, providing a strong platform for future growth.

Unicycive continues to explore additional partnership opportunities in Asia and Europe to further expand its market presence and accelerate the commercialization of Oxylanthanum Carbonate. The company aims to establish a global network of strategic partners to bring innovative treatments to patients with kidney disease worldwide.

Source: Company Documents

As with any company focusing on creating solutions for health issues, navigating the regulatory maze is critical for success. Unicycive has demonstrated a strong ability to do so.

Oxylanthanum Carbonate

The company's lead program, Oxylanthanum Carbonate (OLC), is on a significantly de-risked regulatory pathway for commercialization. In a Type C meeting with the FDA in Q4 2021, the company received clear guidance to file a New Drug Application (NDA). Unicycive is pursuing a 505(b)(2) pathway for U.S. approval, leveraging pre-clinical and clinical data from the approved lanthanum-containing phosphate binder, Fosrenol. This pathway allows the company to skip certain clinical trial phases, streamlining the approval process.

The company conducted a bioequivalence (B.E.) study comparing urinary phosphorus changes between OLC and Fosrenol in healthy volunteers and a 6-month oral toxicity study in mice. The results showed that OLC met all endpoints, indicating its safety and efficacy. Additionally, the company completed standard studies on manufacturability and commercial supply readiness. Unicycive completed the B.E. study with volunteers in Q4 2022 and is on track to file the NDA in mid-2023.

With a one-year review process, potential FDA approval could be anticipated in 2024. 

Oxylanthanum Carbonate regulatory strategy and key milestones

FDA Regulatory Strategy

• 505(b)(2) regulatory pathway for the potential U.S. approval of OLC.

• Leverage pre-clinical and clinical data from Fosrenol to support NDA.

• Bioequivalence study in healthy volunteers comparing urinary phosphorus changes between OLC and Fosrenol.

• 6-month oral toxicity study in mice.

• Treatment-emergent adverse events were comparable between the OLC and Fosrenol groups, with no serious adverse events or deaths reported. 

Commercial strategy

• Product positioning, market access, and market shaping activities are ongoing to optimize the value proposition.

• Pursuing a parallel commercial model to address the concentrated nephrology market, including partnerships with pharmaceutical companies, license and/or distribution agreements with dialysis organizations, and outsourced contract sales organizations. 

*OLC is an unapproved investigational new drug being developed under FDA’s 505(b)(2 ) regulatory procedure. If approved, OLC will share the same product label and prescribing information as the approved reference-listed drug (RLD) Fosrenol, with the advantage of smaller, immediate-release tablets that are swallowed whole and not chewed.

UNI-494

Unicycive's other program, UNI-494, is also positioned well for a shorter approval timeframe. As a novel pro-drug of a marketed agent, nicorandil, it uses an established legacy with known MOAs and demonstrated safety and efficacy with its use of nitric oxide. It uses a known and safe chemical linker, and its controlled release of the active drug in plasma may enable once-daily QD dosing. 

The clinical development of UNI-494 began in the United Kingdom (U.K.) to expedite the process. The company filed a Clinical Trial Application (CTA) with the Medicines and Healthcare Products Regulatory Agency (MHRA) in the U.K. to initiate a Phase I healthy volunteer study. In addition, Unicycive filed an Investigational New Drug (IND) application with the FDA, and a Phase II proof-of-concept (POC) study is expected in the second half of 2023.

While nothing is guaranteed during this process, Unicycive Therapeutics is taking intelligent steps that could lead to commercialization in a shorter timeframe compared to many other companies in the industry.

Source: Company Documents

Unicycive Therapeutics focuses on developing drug candidates for serious kidney diseases. Its lead program, Oxylanthanum Carbonate (OLC), aims to address the challenging problem of uncontrolled hyperphosphatemia with a patient-friendly solution. This serious complication often affects patients undergoing dialysis and can lead to significant health risks if not managed effectively.

Hyperphosphatemia is strongly associated with mortality and hospitalization

Mineral Medbolism, Mortality, and Morbidity in Maintenance Hemodialysis | Geoffrey A. Block, Preston S. Klassen, J. Michael Lazarus, Norma Ofsthun. Edmund G Lowrie and Glenn M. Chertow | JASN August 2004, 15 (8) 2208-2218; DOI: https://journals.lww.com/jasn/abstract/2004/08000/mineral_metabolism,_mortality,_and_morbidity_in.26.aspx

Source: Company Documents

Oxylanthanum Carbonate (OLC) Product Profile

• Oxylanthanum Carbonate (OLC) is a novel phosphate binder designed to treat hyperphosphatemia in patients with chronic kidney disease (CKD).

• The mechanism of action involves binding to dietary phosphate in the gastrointestinal (GI) tract, which is then excreted via the feces, resulting in reduced serum phosphate levels.

• Unicycive's proprietary nanotechnology allows more active medication to be packed into smaller pills, offering greater convenience and efficacy for patients.

• Key Features of OLC

  • Enhanced surface area due to proprietary nanotechnology

  • Lower molecular weight

  • Immediate-release tablets

  • Smaller pills that are swallowed whole (Not Chewed)

UNI-494 is Unicycive Therapeutics' other program, targeting Acute Kidney Injury (AKI). This drug is designed to focus on mitochondria—the "powerhouse of the cell"—which play a critical role in energy production and cellular health. Mitochondrial dysfunction can lead to kidney damage, which UNI-494 aims to address by regulating mitochondrial activity.

Source: Company Documents

UNI-494 restores mitochondrial function mechanism of action

• A hallmark feature of mitochondrial dysfunction is the chronic opening of MPT Pores and the overproduction of Reactive Oxygen Species (ROS)

• Chronic opening of MPT Pore leads to water and solute influx, injury, and subsequent death

• UNI-494 is an ATP-sensitive K channel (KATP) activator

• Binds to SUR2 subunit of KATP channel that, in turn, leads to closing of MPT pores

• Nicorandil down-regulates the production of ROS

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