What changed in this filing

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Item 1. Business

2025-04-15 compared with 2024-03-27 · 312 added, 886 removed, 909 unchanged (57% of the section changed)

are a clinical-stage biopharmaceutical company focused on delivering groundbreaking therapies using our lipid nanocrystal (LNC) platform

delivery technology (LNC Platform).

We are seeking to develop an internal pipeline of products utilizing the LNC Platform to successfully

encapsulate small molecules and small oligonucleotides and facilitate targeted and extrahepatic delivery to desired cells and tissues

without toxicity.

In addition, we believe the LNC Platform can also support building an external pipeline of products for leading pharmaceutical

companies seeking to develop novel formulations that capitalize on the unique characteristics of the LNC Platform to facilitate, enhance

and optimize the delivery of complex molecules, including small molecules, antisense oligonucleotides (ASOs) and silencing or short interfering

RNAs (siRNAs).

current lead product candidate is MAT2203 (oral amphotericin B), a highly potent antifungal drug which, by virtue of LNC delivery, has

been made oral, safe, and well-tolerated for prolonged administration in patients with life-threatening invasive fungal infections.

the successful EnACT Phase 2 trial in the treatment of cryptococcal meningitis, MAT2203 is now positioned for a single, Phase 3 registration

trial (the ORALTO trial) in support of a New Drug Application (NDA) for the treatment of invasive aspergillosis in patients with limited

treatment options.

internal discovery programs are currently directed at:

safe and effective delivery of chemotherapeutic agents for oncology applications;

formulation and delivery of small oligonucleotides, such as antisense oligonucleotides (ASOs) and silencing or short interfering

RNAs (siRNAs), with a primary therapeutic focus on inflammation.

are dedicated to maximizing the value associated with our unique LNC Platform.

This proprietary platform technology, which partially

relies upon an exclusive worldwide license from Rutgers University to certain intellectual property, nano-encapsulates chemical and biological

payloads in a manner that facilitates safe, efficient, and targeted intracellular delivery for a wide variety of molecules.

been used to successfully deliver a variety of therapeutic compounds in vivo, including small molecules, peptides, proteins, and small

oligonucleotides.

Importantly, LNCs are well differentiated from other lipid nanoparticle delivery technologies.

LNCs are primarily comprised of phospholipids, like phosphatidylserine (PS), calcium (which is required to keep LNCs intact) and a designated

therapeutic cargo, which is trapped inside or between the bilayers of the LNC, resulting in a highly stable, crystalline structure which

protects the cargo and allows for oral administration surviving gastrointestinal conditions.

Outside of cells, such as in gastrointestinal

fluid and in blood, normal extracellular levels of calcium maintain this crystalline structure, whereas in tissues LNCs are avidly taken

up by professional phagocytes, as well as infected, inflamed, and malignant cells.

In the much lower calcium environment of the cytosol,

LNCs lose their crystalline structure and release their cargo intracellularly.

have a novel targeting profile utilizing PS to facilitate both membrane fusion and PS-receptor mediated endocytosis.

Depending on the

therapeutic target being approached, the cargo may either have a direct impact inside that particular cell, or, alternatively blood cells

such as neutrophils can act as a vehicle to indirectly deliver cargo to target tissues, as in the case of infection or inflammation.

LNCs also have a neutral immunogenic profile enabling repeated administration, unlike lipid nanoparticle (LNP) delivery, which because

of inherent cytotoxicity may also not be amenable to repeat administration.

Uniquely, the highly stable structure of LNCs permits oral

administration (not possible with LNPs) since the cargo is protected within the LNC structure from the harsh environment of the gastrointestinal

and clinical studies have consistently demonstrated that orally administered LNCs can successfully deliver therapeutic cargos in vivo ,

to sites of infection, to areas of inflammation, and to tumors.

All these target tissues have cells with PS exposed on their surface

(which creates opportunities for direct fusion with the cell membrane), as well as specific PS-recognizing receptors on tissue-resident

professional phagocytes (which facilitates additional cellular uptake via endocytosis).

The ability to target diseased tissues –

and potentially avoid off-target effects - the capability to enter cells via both fusion and endocytic mechanisms, and the ability of

LNCs to encapsulate – and deliver - a broad range of therapeutic agents provides a solid foundation from which to create a broad

pipeline of internal product candidates and external partnerships.

While the delivery of therapeutic nucleic acids has advanced considerably

in recent years, to date there has been little progress in orally delivered oligonucleotide therapeutics beyond conjugated oligos specifically

targeting the liver.

Similarly, there are also significant potential opportunities for both small molecules (with potential for both

enhanced safety and increased efficacy) and small oligonucleotides in the oncology area.

BioPharma Holdings, Inc.

(“Matinas” or the “Company”) is a clinical-stage biopharmaceutical company focused on

delivering groundbreaking therapies using our lipid nanocrystal (“LNC”) platform delivery technology (LNC Platform).

lead product candidate is MAT2203 (oral amphotericin B), a highly potent antifungal drug which, by virtue of LNC delivery, has been made

oral, safe, and well-tolerated for prolonged administration in patients with life-threatening invasive fungal infections.

Following the

successful EnACT Phase 2 trial in the treatment of cryptococcal meningitis, MAT2203 is now positioned for a single, Phase 3 registration

trial (the “ORALTO trial”) in support of a New Drug Application (“NDA”) for the treatment of invasive aspergillosis

in patients with limited treatment options.

had also been seeking to develop an internal pipeline of products utilizing the LNC Platform to successfully encapsulate small molecules

and small oligonucleotides and facilitate targeted and extrahepatic delivery to desired cells and tissues without toxicity, with a focus

on small molecule oncology applications as well as the formulation and delivery of small oligonucleotides with a primary therapeutic

focus on inflammation.

an 80% reduction in workforce implemented in late October 2024, the Company implemented a cost-cutting strategy and paused further

clinical development of MAT2203 while continuing to engage in dialogue with prospective partners for the product with the goal of

consummating a licensing, sale or other similar transaction as soon as possible to advance the development of MAT2203 into Phase 3.

In addition, the Company continues to engage with the FDA to keep the MAT2203 Investigational New Drug Application

(“IND”) active and is actively maintaining and prosecuting intellectual property relating to MAT2203 and to the LNC

Platform generally as well as maintaining all of its obligations under our license agreement with Rutgers University.

continue to support the patients in our Expanded/Compassionate Use Access Program with the assistance of outside medical clinician

As a result of the reduction in force, the Company has paused the internal development of a pipeline of products

utilizing the LNC Platform as it evaluates strategic alternatives for those early-stage programs in oncology and inflammatory

We remain engaged in an ongoing partnership process

for MAT2203, seeking one or more development and/or commercialization partners.

We will require either (i) the consummation of a partnership

transaction, or (ii) raising additional capital, prior to commencing the ORALTO trial.

In the event a partnership is consummated, the

partner may seek to revise the ORALTO trial or could determine a completely new development program and pathway for MAT2203.

be no assurance that the Company will be successful in consummating a transaction involving MAT2203.

September 21, 2023, Matinas Biopharma Holdings, Inc.

(the “Company”) received

a deficiency letter (the “Letter”) from the NYSE American LLC (the “NYSE

American” or the “Exchange”) indicating that the Company is not in compliance

with the NYSE American continued listing standard set forth in Section 1003(f)(v) of the

NYSE American Company Guide due to its shares of common stock selling for a substantial period

of time at a low price per share, which NYSE American determined to be a 30 trading day average

price of less than $0.20 per share.

On March 22, 2024, Matinas BioPharma Holdings, Inc.

“Company”) announced that on March 21, 2024, the Company received a letter from

the NYSE American LLC (the “NYSE American”) indicating that the Company had regained

compliance with the NYSE American continued listing standard set forth in Section 1003(f)(v)

of the NYSE American Company Guide due to its shares of common stock demonstrating sustained

price improvement.

November 1, 2023, at the 2023 annual meeting of stockholders of the Company, the stockholders

approved the authorization of the Board of Directors (the “Board”), in its sole

and absolute discretion and without further stockholder approval, to (i) reduce the total

number of authorized shares of the Company’s Common Stock, from 500,000,000 to 250,000,000

(the “Authorized Share Reduction”), and (ii) effect a reverse stock split of

the Common Stock at a ratio to be determined by the Board ranging from a ratio of one-for-two

(1:2) to a ratio of one-for-fifty (1:50).

February 2024, we announced agreement with the United States Food and Drug Administration

(“FDA”) on the design of a single Phase 3 registration trial of MAT2203 in patients

with invasive aspergillosis who have limited treatment options, including consensus on all

critical elements of the ORALTO trial.

March 2024, we announced that the Company would require either (i) the consummation of a

partnership transaction, or (ii) raising significant additional capital, prior to commencing

the ORALTO trial.

The Company continued to support (a) the ongoing MAT2203 Compassionate/Expanded

Use Access Program, (b) all MAT2203 regulatory requirements, (c) the prosecution and maintenance

of all intellectual property relevant to MAT2203 and the LNC Platform and (d) the early stage

research and development of other applications of the LNC Platform in the oncology and inflammation

April 2, 2024, we announced entry into a securities purchase agreement (the “April

2024 Purchase Agreement”), with certain institutional investors (collectively, the

“April 2024 Purchasers”).

The April 2024 Purchase Agreement provided for the

sale and issuance by the Company of (i) 666,667 shares (the “April 2024 Shares”)

of the Company’s common stock, $0.0001 par value per share (the “April 2024 Common

Stock”) and warrants to purchase up to 666,667 shares of Common Stock (the “Warrants”

and, together with the April 2024 Common Stock, the “April 2024 Securities”).

The offering price per share and accompanying warrants was $15.00.

The April 2024 Warrants

have an exercise price of $17.50 and were exercisable beginning October 2, 2024, and expire

on the five-and-a-half year anniversary of the date of issuance.

The offering resulted in

gross proceeds to the Company of approximately $10 million before deducting placement agent’s

fees and related offering expenses.

August 20, 2024, pursuant to the NYSE American’s Compliance Guidance Memo which requires

ten calendar days public notice for certain corporate actions, the Company announced that

the Board approved the Authorized Share Reduction and a reverse stock split of the Common

Stock at a ratio of one-for-fifty (1:50) (the “Reverse Stock Split”), which would

become effective at 5:00PM (EST) on August 30, 2024.

August 27, 2024, the Company received notice that trading of its shares of Common Stock had

been halted by the NYSE American due to its low trading price.

The trading halt remained

in effect until after the Company consummated the communicated reverse stock split of the

Common Stock and the market opened on September 3, 2024.

August 30, 2024, the Authorized Share Reduction and the Reverse Stock Split became effective

(EST) and the shares of Common Stock began trading on the split-adjusted basis

under the Company’s existing trading symbol, “MTNB,” when the market opened

on September 3, 2024.

October 31, 2024, we announced that negotiations under a non-binding term sheet with a single

partner for global licensing rights to develop, manufacture and commercialize MAT2203 for

all future treatment indications (the “MAT2203 Term Sheet”), including the intended

initial indication of treatment for patients with invasive aspergillosis with limited or

no other treatment options, were terminated following notification from the perspective partner

for reasons unrelated to MAT2203.

As a result, we implemented an immediate 80% workforce

reduction, eliminating 15 positions, including three members of senior management, and ceased

certain product development activities to preserve cash while we evaluated a potential sale

of MAT2203 and/or other strategic alternatives, including a potential winddown or dissolution

of the Company.

January 6, 2025, we announced that we received a deficiency letter (the “ January 2025

NYSE Notice”) from the NYSE American stating that the Company failed to hold an annual

meeting of stockholders during the fiscal year ended December 31, 2024, as required by Section

704 of the Company Guide.

The January 2025 NYSE Notice has no immediate impact on the listing

of the Company’s common stock, which will continue to be listed and traded on the NYSE

American during the applicable cure period but will be assigned a “.BC” indicator

by the NYSE to indicate that the Company is below compliance.

The “.BC” indicator

will be removed at such time as the Company is deemed compliant with the NYSE’s continued

listing standards.

The Company intends to hold its annual meeting no later than December

31, 2025 in order to regain compliance under the Company Guide.

February 13, 2025, we announced that the Company entered into a securities purchase agreement

(the “February 2025 Agreement”) with a certain group of investors (the “February

2025 Investors”), pursuant to which they agreed to purchase from the Company 3,300

shares of Series C Convertible Preferred Stock (the “Preferred Stock”) and warrants

to purchase up to 11,262,808 shares of common stock (the “February 2025 Warrants”)

at a purchase price of $1,000 per share of Preferred Stock and accompanying warrants for

aggregate gross proceeds of $3.3 million before deducting offering expenses payable by the

The February 2025 Investors purchased 1,650 shares of Preferred Stock and accompanying

warrants to purchase up to 5,631,404 shares of common stock for gross proceeds to the Company

of $1.65 million at an initial closing on February 13, 2025.

Subject to the satisfaction

of certain closing conditions, the Investors paid an additional $1.65 million

in exchange for an additional 1,650 shares of Preferred Stock and accompanying warrants to

purchase up to 5,631,404 shares of common stock at a second closing on April 8, 2025.

The shares of Preferred

Stock will be convertible into common stock at a conversion price of $0.586, and each share

of Preferred Stock is initially convertible into 1,706 shares of common stock.

will have an exercise price of $0.6446 per share, will be exercisable, subject to certain

exceptions, beginning on the effective date of the Shareholder Approval and will expire five

years from the effective date of the Shareholder Approval.

funds will be used for general corporate purposes, with a focus on reducing operating expenses and exploring strategic alternatives for

MAT2203, the Company’s Phase 3-ready antifungal drug candidate for the treatment of invasive fungal infections, as well as other

strategic alternatives for the Company.

In connection with the February 2025 Agreement, Dr.

Smith, MD, MBA has been appointed

to the Board of Directors.

March 3, 2025, we filed a Notice of Special Meeting of Stockholders to be held on April 4,

2025 (the “Special Meeting).

At the Special Meeting, stockholders will act on the following

(1) to approve, for purposes of complying with the applicable provisions of Section

713 of the NYSE Company Guide (a) the issuance of up to an aggregate of 16,894,212 shares

of common stock upon the conversion of the Preferred Stock and the exercise of the February

2025 Warrants (the “Stock Issuance Proposal”), and (b) the terms thereof, which

may constitute a “Change of Control” as defined in the NYSE Company Guide;

(2) to ratify the appointment of EisnerAmper LLP as our independent registered public accounting

firm for the year ended December 31, 2025.

lead drug candidate based on the LNC Platform is MAT2203, an oral formulation of amphotericin B, a well-known and highly effective antifungal

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therapy, and, most recently with an Orphan Designation for the treatment of cryptococcosis.

We plan to pursue additional orphan designations

for the treatment of aspergillosis, the treatment of invasive candidiasis and the treatment of certain endemic mycoses.

Upon approval,

MAT2203 could be eligible for up to 12 years of regulatory or marketing exclusivity in the United States.

initial indication for MAT2203 is early step-down therapy from IV amphotericin B for the treatment of invasive aspergillosis in patient

with limited treatment options.

Invasive aspergillosis is a serious and life-threatening invasive fungal infection that occurs primarily

in severely immunocompromised patients with hematological malignancies and in transplant recipients.

This initial step-down indication

is a gateway indication, as we plan to expand the utilization of MAT2203 into the treatment of other invasive fungal infections (IFIs)

and potentially even for prophylaxis against IFIs in immunocompromised patients, such as transplant patients.

We believe that it is possible to pursue

additional orphan designations for the treatment of aspergillosis, the treatment of invasive candidiasis and the treatment of certain

endemic mycoses.

Upon approval, MAT2203 could be eligible for up to 12 years of regulatory or marketing exclusivity in the United States.

initial planned indication for MAT2203 is early step-down therapy from IV amphotericin B for the treatment of invasive aspergillosis

in patient with limited treatment options.

Invasive aspergillosis is a serious and life-threatening invasive fungal infection that occurs

primarily in severely immunocompromised patients with hematological malignancies and in transplant recipients.

This initial step-down

indication is a gateway indication, as we believe that a partner could expand the utilization of MAT2203 into the treatment of other

invasive fungal infections (IFIs) and potentially even for prophylaxis against IFIs in immunocompromised patients, such as transplant

EnACT ( Encochleated Oral Amphotericin for Cryptococcal Meningitis Trial ) Phase 2 study was a Phase 2 prospective, randomized,

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For 40 patients receiving MAT2203 treatment, overall survival

remained at 90% through 18 weeks, while the survival rate at Week 2 was 95% (the primary endpoint for the upcoming Phase 3 registration

trial in cryptococcal meningitis).

remained at 90% through 18 weeks, while the survival rate at Week 2 was 95%.

Importantly, the incidence of adverse events relating to kidney function and anemia were significantly

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trial of MAT2203 in patients with invasive aspergillosis who have limited treatment options, including consensus on all critical elements

of the registrational path for MAT2203 (the ORALTO trial).

is a Phase 3, randomized, multicenter, open-label, adjudicator-blinded study to evaluate the efficacy and safety of MAT2203 as an oral

step-down treatment following treatment with AmBisome® (liposomal IV-amphotericin B) compared with the standard of care in patients

with invasive aspergillosis who have limited treatment options.

The primary efficacy endpoint is all-cause mortality at study day 42.

secondary objectives include:

of the ORALTO trial.

In its correspondence, FDA agreed that the ORALTO trial would potentially be sufficient to support

the registration of MAT2203 for an initial indication for the treatment of invasive aspergillosis in patients with limited treatment options,

when and if conducted.

Approval would be subject to normal FDA review of all aspects of this clinical trial.

is planned to be a Phase 3, randomized, multicenter, open-label, adjudicator-blinded study to evaluate the efficacy and safety of MAT2203

as an oral step-down treatment following treatment with AmBisome® (liposomal IV-amphotericin B) compared with the standard of care

in patients with invasive aspergillosis who have limited treatment options.

The primary efficacy endpoint would be all-cause mortality

at study day 42.

secondary objectives would include:

2020;71(5):e45-49

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of the impact of MAT2203 on healthcare resource utilization and quality of life impact.

is expected to include approximately 216 adults with recently diagnosed probable or proven invasive aspergillosis who are being treated

with AmBisome due to their inability to receive an IV mold-active azole and with limited alternative treatment options.

to two days of initial treatment with AmBisome, eligible study participants will be entered into the study and randomized in a 2:1 ratio

to receive either oral MAT2203 or continued AmBisome treatment followed by standard of care.

study participants will receive up to 12 weeks of treatment starting from the first day of treatment with AmBisome.

has been planned to include approximately 216 adults with recently diagnosed probable or proven invasive aspergillosis who are being

treated with AmBisome due to their inability to receive an IV mold-active azole and with limited alternative treatment options.

up to two days of initial treatment with AmBisome, eligible study participants would be entered into the study and randomized in a 2:1

ratio to receive either oral MAT2203 or continued AmBisome treatment followed by standard of care.

study participants would receive up to 12 weeks of treatment starting from the first day of treatment with AmBisome.

It is anticipated

that all study participants will be hospitalized during the initial AmBisome treatment period.

that all study participants would be hospitalized during the initial AmBisome treatment period.

After step-down to oral MAT2203, study

participants may be discharged from the hospital to continue treatment on an outpatient basis, as clinically appropriate.

independent Data Review Committee, who will be blinded to treatment, will adjudicate primary and secondary endpoints, including clinical,

independent Data Review Committee, who will be blinded to treatment, would adjudicate primary and secondary endpoints, including clinical,

radiological, and mycological responses.

Once approximately 75% of participants are enrolled, an independent Data Safety Monitoring Board

will review the overall pooled all-cause mortality rate in a blinded fashion to ensure that the sample size assumptions are reasonable

would review the overall pooled all-cause mortality rate in a blinded fashion to ensure that the sample size assumptions are reasonable

and that the study is adequately powered.

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can be made to the trial.

will be conducted at approximately 65 investigator sites in the U.S., Europe, South America, Middle East, and Asia Pacific.

is expected to commence in the second half of 2024 and is expected to require approximately 24 months.

are actively engaged in an ongoing partnership process for MAT2203, seeking one or more development and/or commercialization partners.

We will require either (i) the consummation of a partnership transaction, or (ii) raising additional capital, prior to commencing the

ORALTO trial.

was planned to be conducted at approximately 65 investigator sites in the U.S., Europe, South America, Middle East, and Asia Pacific.

Enrollment is expected to require approximately 24 months, if commenced.

remain engaged in an ongoing partnership process for MAT2203, seeking one or more development and/or commercialization partners.

require either (i) the consummation of a partnership transaction, or (ii) raising additional capital, prior to commencing the ORALTO

In the event a partnership is consummated, the partner may seek to revise the ORALTO trial or could determine a completely new

development program and pathway for MAT2203.

There can be no assurance that the Company will be successful in consummating a transaction

involving MAT2203.

addition to conducting the EnACT trial, a MAT2203 Compassionate/Expanded Use Access Program was established to provide MAT2203 on a compassionate

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patient has a reasonable life expectancy, and their underlying conditions are under control.

patients to date have been enrolled in the Program at multiple healthcare institutions, including the University of Michigan, Johns Hopkins,

Nationwide Children’s Hospital, City of Hope, Vanderbilt University Medical Center, the National Institutes of Health, Children’s

Hospital of Philadelphia, Memorial Sloan Kettering Cancer Center, and the University of California, San Diego School of Medicine.

majority of enrolled patients are post-transplant or are undergoing treatment for underlying malignancies.

The infections being treated

with MAT2203 include a variety of micro-organisms (including Aspergillus , Mucorales species , Candidiasis , Fusarium

and suspected Coccidioides ) occurring at multiple sites of infection, including brain, bladder/colon, bone, lung, sinus, and

Most patients were receiving AmBisome® prior to enrollment but developed treatment-limiting nephrotoxicity and most also required

treatment for either azole-resistant organisms or had clinically failed azole therapy and had no other treatment options.

the 19 patients enrolled in the Program, 15 have available follow-up and 4 recently initiated or will soon commence treatment with MAT2203.

of the 15 patients had either complete clinical resolution or objective improvement in clinical markers of infection (including radiologic

and mycologic).

the 5 patients who completed their full individually specified course of treatment (ranging from 2 weeks to 1 year, depending on

the infection) - all have had complete clinical resolution with no relapses or recurrence of their infection.

additional patients have shown objective improvement in clinical markers and are continuing treatment with MAT2203 as planned.

of the 15 patients were unable to complete their individually specified course of treatment, although 2 saw significant clinical

improvement of their fungal infection and are included in the 12 overall successful cases.

patients transitioned to palliative care shortly after starting therapy with MAT2203 because of unanticipated progression of their

malignant disease.

patient discontinued therapy after two days due to underlying GI issues (i.e., Crohn’s disease).

patient passed away due to progression of their underlying disease approximately 8 weeks into therapy (but previously experienced

significant clinical improvement of their fungal infection).

patient discontinued MAT2203 treatment following 10 weeks of therapy due to underlying GI issues (long-standing nausea/vomiting),

but with improvement in their fungal infection.

total of 37 patients to date have been enrolled in the Program at multiple healthcare institutions, including the University of Michigan,

Johns Hopkins, Nationwide Children’s Hospital, City of Hope, Vanderbilt University Medical Center, the National Institutes of Health,

Children’s Hospital of Philadelphia, Memorial Sloan Kettering Cancer Center, and the University of California, San Diego School

The majority of enrolled patients are post-transplant or are undergoing treatment for underlying malignancies.

patients have been treated for invasive asperillosis, each with positive results.

The infections being treated with MAT2203 include a

variety of micro-organisms (including Aspergillus , Mucorales species , Candidiasis , Fusarium and suspected

Coccidioides ) occurring at multiple sites of infection, including brain, bladder/colon, bone, lung, sinus, and skin.

Most patients

were receiving AmBisome® prior to enrollment but developed treatment-limiting nephrotoxicity and most also required treatment for

either azole-resistant organisms or had clinically failed azole therapy and had no other treatment options.

the 15 patients enrolled in the Program who completed treatment with MAT2203 (median treatment of 16 weeks with a range of 2 to 49 weeks),

8 had a complete response and 7 were improved.

Response to treatment was assessed by the treating physician.

Nine additional patients

continued to receive longer-term treatment with positive ongoing effects and 5 initiated treatment in the third and fourth quarter of

To date, only 2 patients have discontinued MAT2203, both occurring during the first week of treatment, with one due to an intolerance

and the other due to a terminal condition not otherwise related to the underlying fungal infection.

all patients who experienced renal toxicity following treatment with AmBisome saw their renal function return to baseline after transitioning

to MAT2203 therapy and suffered no further renal side effects over the course of extended treatment with MAT2203.

Platform Work

addition to advancing MAT2203 into the ORALTO Phase 3 trial, we continue to expand the utilization of the LNC Platform with small molecules

and small oligonucleotides outside of infectious disease, targeting inflammation and oncology.

are investigating a variety of LNC formulations of two small oligonucleotides designed to target inflammatory cytokines IL-17A and TNFα

and have conducted a series of in vitro and in vivo studies evaluating the biological activity associated with oral delivery

as well as the corresponding associated clinical benefit of IL-17A knockdown in an imiquimod (IMQ) induced murine psoriasis disease model.

preliminary studies have documented biological activity in the form of cytokine knockdown and have also provided some evidence of associated

tangible clinical benefit with improvements in skin lesion appearance (redness, scaling) in this qualitative psoriasis model.

remain under evaluation and the analyses are focused on (a) clarifying the strength and time course of cytokine inhibition, and (b) evaluating

cytokine mRNA levels and specific tissue responses in these models to better understand and interpret these data.

December 2023, we announced results from a series of in vivo studies demonstrating successful oral delivery of two LNC-formulated

small single-strand oligonucleotides that specifically target key inflammatory cytokines TNFα and IL-17A in well-established and

validated animal models that mimic acute inflammatory responses seen in human diseases.

Colitis Study (“TNFα”)

dextran sulfate sodium (“DSS”)-induced murine colitis model was used to evaluate an orally administered LNC-delivered small

oligonucleotide that specifically targets TNFα mRNA synthesis.

Colon tissue TNFα mRNA levels, as assessed by quantitative

real-time PCR analysis, were lower following orally administered active LNCs, resulting in statistically significant reductions of serum

TNFα levels by 37% compared with diseased, but untreated animals.

Importantly, clinical disease activity scores at key time points

in the studies were also significantly improved with an active LNC formulation.

Psoriasis Study (“IL-17A”)

imiquimod (“IMQ”)-induced murine psoriasis model was used to evaluate an orally administered, LNC-delivered small oligonucleotide

designed to inhibit IL-17A mRNA synthesis, which contributes significantly to the progression of psoriatic skin lesions.

Similar to the

DSS colitis model, skin tissue levels of IL-17A mRNA in the IMQ psoriasis model were lower with orally administered active LNCs compared

with IMQ alone.

In this model, while IL-17A serum levels were not expected to change, improvement was demonstrated in clinical disease

markers of skin redness and scaling, further validating the biological activity of these small oligonucleotides.

November of 2023 we announced positive results from an in vivo animal study of an oral LNC formulation of docetaxel, a well-known

chemotherapeutic agent used in the management of multiple metastatic and unresectable tumors.

Anti-tumor effects of daily oral LNC-docetaxel

were comparable to IV-docetaxel with statistically significant reductions in tumor volume compared with untreated controls at Day 14

(high dose oral LNC -63%;

low dose oral LNC -57%;

IV docetaxel -68%), and similar reductions in tumor weight at Day 14.

No systemic toxicities

Body weight was stable over treatment duration and hematologic parameters were similar to untreated controls.

March 2024 we announced positive results from an additional in vivo study of LNC-docetaxel in healthy mice.

The goal of the study was

to determine whether an oral LNC formulation of docetaxel could improve the overall safety profile of conventional IV-administered docetaxel.

The study included 24 healthy BALB/c mice divided into three treatment groups:

(1) control animals treated with oral saline, (2) IV-docetaxel

(30 mg/kg, or 0.6 mg/dose) administered once a week for three weeks, and (3) oral LNC-docetaxel (37.5 mg/kg, or 0.75 mg/dose) administered

once daily over three weeks.

The primary endpoint of the study was change in body weight over the treatment period which how toxicity

is primarily manifested in this model.

takeaways included the following:

Day 22, the total amount of docetaxel administered with the oral LNC-docetaxel formulation was more than 8x greater than with IV-docetaxel

(the final IV dose was used to measure pharmacokinetics).

mice treated with IV-docetaxel lost a significant amount of weight (toxicity), with an average peak loss of 20% of their

original body weight.

treated with oral LNC-docetaxel maintained their body weight, which was statistically no different than the weight of control mice

treated with oral saline.

mouse in the IV-docetaxel group died prior to the conclusion of the study and was censored from the analysis (last measurement was

-32% body weight loss);

the curve of the IV-docetaxel group also reflects the expected 7-day recovery following an IV dose of docetaxel.

daily administered oral LNC-docetaxel dose was 50% higher, and the total amount of drug administered was 3.5 times greater, than

the LNC-docetaxel dose administered in a previous study that demonstrated anti-tumor activity comparable to IV-docetaxel in a syngeneic

mouse melanoma model.

steps include evaluating the efficacy of the current LNC-docetaxel formulation in other tumor models.

Additionally, we plan to evaluate

the potential anti-tumor activity of LNC formulations of small oligonucleotides.

are focused on redefining the intracellular delivery of nucleic acids and small molecules through our LNC Platform and its application

have been focused on redefining the intracellular delivery of nucleic acids and small molecules through our LNC Platform and its application

to overcome current challenges in safely and effectively delivering small molecules, nucleic acids, gene therapies, proteins/peptides,

and vaccines.

elements of our strategy include:

MAT2203 into the ORALTO trial for the treatment of invasive aspergillosis in patients with limited treatment options by securing

a development and/or commercial partner.

This initial indication is designed to be a gateway indication to establish the pharmacodynamic

bridge necessary to expand the use of MAT2203 into other indications to treat deadly invasive fungal infections (e.g., mucormycosis,

candidiasis and the endemic mycoses) through limited additional clinical work under a 505(b)(2) pathway, thereby making MAT2203 a

pipeline in a product.

the utilization of our LNC Platform with other small molecules and small oligonucleotides into inflammation and oncology in order

to develop an internal pipeline of differentiated drug candidates.

Oral, extrahepatic and non-toxic intracellular delivery of these

molecules would represent a significant advancement.

an external pipeline of collaborations focused on our LNC Platform with leading pharmaceutical companies to provide delivery solutions

for their complex small molecules and small oligonucleotides, including ASOs and siRNAs.

Lipid Nanocrystal (LNC) Platform

efficient, and targeted intracellular delivery of medicines remains one of the biggest challenges in the pharmaceutical and biotech industry

An ever-growing understanding of the complex biology within cells has given rise to increasingly sophisticated therapeutic approaches

targeting the genetic machinery driving metabolic activity within cells.

However, challenges remain, especially for small molecules causing

significant toxicity and for therapeutic oligonucleotides in areas including safely and efficiently delivering cargo to the interior

of a cell, delivering to targets beyond the liver and in providing opportunities for longer-term oral delivery to increase convenience

and resulting in a potentially significant pharmacoeconomic impact.

Strategically,

we are seeking to leverage the unique features of the LNC Platform and the biology of phosphatidylserine to extend potential applications

for the intracellular delivery of highly potent, but highly toxic small molecules as well as the oral, target delivery of small oligonucleotides.

lipid cylinders” were originally described in scientific literature as complex, cylindrical, multi-lamellar structures arising

from the addition of Ca ++ to sonicated liposomal preparations of phosphatidylserine (PS) in an aqueous solution, with the

lamellae folded in a spiral, crystalline configuration that excludes water.

When sufficient external calcium is present, these structures

remain in a crystalline state, while the addition of etheylenediaminetetraacetic acid (EDTA) to these preparations (removing the calcium)

results in the loss of the stable spiral crystalline structure ( Figure 1 ).

Cochleate Formation

have developed techniques to embed cargo molecules within cochleates as they are assembled.

These new cargo-carrying structures (termed

lipid nanocrystals, or LNCs ) have been used to successfully deliver several different cargo molecules to cells in vitro and

to animals and humans in vivo .

Because of their exceptional stability (an anhydrous crystalline structure) and unique composition

(PS-containing bilayers), we believe that LNCs are a promising alternative for the intracellular delivery of a variety of small molecules

– proteins, peptides – and small oligonucleotides such as ASOs and siRNA.

In addition, since the normal physiologic levels

of calcium in the gut can maintain their crystalline structure, LNC formulations can also potentially be delivered orally, as the encapsulated

cargo is protected from degradation by harsh environmental conditions or enzymes ( Figure 2 ).

LNCs Encapsulate and Protect their Cargo in a Water-free Environment

of Phosphatidylserine

Phosphatidylserine

(PS) is present in virtually all cells and is an integral part of the cell membrane.

PS is normally localized to the inner part of the

membrane bilayer by active cellular processes and not normally exposed externally ( Figure 3 ).

However, when cells are injured

and/or apoptotic, PS moves from the inner layer to the outer layer and is the primary “eat me” signal driving efferocytotic

clearance of apoptotic cells by professional phagocytes.

with cargo carrying LNCs have documented both a lack of cargo accumulation in the tissues of normal, healthy animals, and significant

cargo delivery to involved tissues in infected animals.

Another important aspect of the underlying stability of LNCs is that they do

not release their cargo within the blood (due to the presence of stabilizing levels of calcium), and delivery of cargo is confined to

involved cells and tissues.

Mechanistically,

the cellular entry of LNCs is driven by PS, which is an important participant in both efferocytotic clearance of apoptotic cells and

in physiologic cellular fusion processes ( Figure 3 ).

As noted, apoptotic cells expressing PS on their surface are recognized and

cleared by professional phagocytes, without eliciting the normal inflammatory responses that might otherwise be anticipated with cell

Professional phagocytes themselves have several very specific PS receptors that facilitate this clearance.

Parenthetically this

mechanism is exploited by enveloped viruses to facilitate viral uptake by immune cells – “viral apoptotic mimicry”

– noting that the “envelope” of enveloped viruses is basically comprised of PS.

Thus, phagocytosis of LNCs by professional

phagocytes (and some non-professional phagocytes) becomes one mechanism for intracellular delivery of LNCs.

Importance of Phosphatidylserine (PS) in apoptotic phagocytosis

described above, in addition to its role as an “eat-me” signal for uptake of apoptotic cells by phagocytes, PS also plays

a very important role in normal physiologic cellular fusion processes – as a “fuse-me” signal (such as with the formation

of myotubules from myoblasts, the formation of osteoclasts from osteoblasts, and the fertilization of an of egg by sperm to form a zygote)

or even as a “heal me” signal (as with axonal fusion after injury or repair of injured cell membranes).

Consequently, the

presence of PS on both the surface of LNCs and on the surface of targeted somatic cells (which themselves may express PS because of injury

or inflammation) creates additional opportunities for intracellular delivery via direct cellular fusion ( Figure 4 ).

4 – Importance of Phosphatidylserine (PS) in Cellular Fusion

Drug Delivery

of their underlying stability, LNCs do not release cargo within the blood (due to the presence of stabilizing levels of calcium), and

the delivery of cargo is confined to involved cells and tissues.

Studies utilizing an LNC formulation of radio-labeled amphotericin showed

no accumulation in normal healthy tissues, in contrast to multiple studies showing clinically meaningful tissue levels of amphotericin

when amphotericin-carrying LNCs were administered in the setting of systemic fungal infections.

oral administration, LNCs are transported across the cells lining the gastrointestinal tract (via transcytosis).

Because of their size,

LNCs do not enter the portal circulation and thereby avoid first pass hepatic metabolism.

Instead, they are transported through the gut

lymphatics to the thoracic duct and enter the circulatory system via the superior vena cava.

Once they have entered the circulation,

LNCs are transported by professional phagocytes (as well as via other non-cellular mechanisms) to sites of injury or infection, where

they are avidly taken up by infected/injured cells that have PS on the outer layer of their cell membranes.

Finally, when exposed to

the very low calcium environment in the interior of a cell, the forces responsible for maintaining the otherwise stable LNC structure

are no longer as strong, and the LNCs release their cargo.

Differentiation

LNPs in blood bind ApoE to their surface and are taken up into cells by clathrin-mediated endocytosis via the ApoE-recognizing LDL receptor.

From within early endosomes, LNPs then act to disrupt the endosomal membrane and gain entry to the cytosol.

Endosomal escape of LNPs

is a very inefficient process, with endosomal escape rates of generally < 5%.

Administration of LNPs can also be associated with injection

site reactions and other toxicities arising from the destruction of the endosomal membrane, which, ultimately, can limit their chronic

Additionally, LNPs cannot be delivered orally.

LNC delivery can overcome many of the limitations of LNPs with oral administration,

extra-hepatic targeting, multiple potential cellular entry mechanisms, a breadth of payload capabilities, the ability to target both

immune and somatic cells, reduced toxicity/improved safety, and opportunities for safe, chronic long-term administration.

Each of these

have been validated with the clinical success of MAT2203 in the treatment of deadly invasive fungal infections.

therapeutic applications of our proprietary delivery technology have focused initially on the delivery of potent, highly effective anti-infective

agents that have treatment-limiting potential toxicities, including irreversible toxic effects on kidney and hearing function.

we have developed a less toxic and orally bioavailable formulation of the potent (but otherwise highly toxic) fungicidal drug amphotericin

B that can be safely used for longer periods of time than currently possible with conventional amphotericin in the treatment of deadly

fungal infections.

This, in turn, has created potential opportunities to use amphotericin B in ways that were not previously possible

with conventional formulations, and create opportunities for amphotericin treatment in settings where conventional amphotericin has proven

to be too toxic, and open the possibilities for much longer-term treatment which should result in overall improved outcomes for patients

with a significant pharmacoeconomic impact.

the observation that LNCs are avidly taken up by innate immune cells (monocytes, neutrophils, and dendritic cells) we believe that

LNCs could become very useful in treating inflammatory diseases.

We have gained access to a number of small oligonucleotides that

are capable of very selectively knocking down individual cytokines – specifically IL-17A and TNFɑ.

successfully advanced the program with these small oligos, first with successful, efficiently encapsulated LNC formulations, and

next with in vitro validation of the efficacy of the LNC formulations.

More recently, we have progressed two of these

LNC-formulated small oligos into in vivo studies in animal disease models, with successful demonstration of both measurable

biological activity and potential therapeutic efficacy in two different models.

In a murine imiquimod-induced psoriasis model we

observed reductions of tissue IL-17A mRNA, accompanied by improvement in skin redness and scaling.

Similarly, in a murine DSS model

of inflammatory bowel disease, daily oral administration of an oral LNC formulation of the TNFɑ targeted oligonucleotide

resulted in reductions of colon TNFɑ mRNA, significant reductions in serum TNFɑ levels, and significant improvements in

disease activity scores.

on the success of MAT2203 in creating a safe, effective formulation of amphotericin that can be administered orally for much longer periods

of time for the treatment of deadly fungal infections, and having seen how avidly tumor cells can take up LNCs in vitro, we have extended

the application of LNC technology to oncology applications.

Some tumors cell lines are also known to have relatively high levels of surface

PS expression, which provides potential directionality for those tumors which may respond positively to treatment with LNC-mediated chemotherapies.

Building upon our experience with MAT2203, there are two specific areas where we believe that LNCs could provide major advances:

for reduced toxicity because of tissue-targeted delivery and low blood levels

for enhanced efficacy through more efficient delivery

began initial formulation work with a number of chemotherapeutic agents, and ultimately chose to move forward with docetaxel.

shown in vitro therapeutic efficacy that proved even better than conventional docetaxel, and moved rapidly to in vivo studies

and into a syngeneic mouse melanoma model (with known high surface PS expression).

In this model, our oral LNC formulation of docetaxel

proved to be equally effective as conventional intravenous docetaxel.

Moreover, despite daily oral administration of the LNC formulation,

there was no adverse impact on body weight, and no indications of any hematologic toxicity.

Through this work, we have demonstrated that

an oral LNC formulation of docetaxel, administered daily, can deliver levels of drug to tumors provide a comparable therapeutic response

to that of conventional IV docetaxel, without any indications of toxicity.

Additional in vivo work in healthy mice has shown that

even higher doses of LNC docetaxel (50% greater) were equally free from toxicity, while similar increases in the IV docetaxel dose were

accompanied by indications of toxicity, with a mean weight loss of approximately 20%.

LNC Clinical Stage Asset:

lead product candidate, MAT2203, is an orally administered LNC formulation of a broad spectrum anti-fungal drug called amphotericin B.

Traditionally, amphotericin B is an IV-administered drug used as a last resort for treatment of systemic fungal infections resistant

to triazoles and echinocandins, including resistant candidiasis, cryptococcal meningoencephalitis, and aspergillosis.

To date, there

have been little to no reported clinically observed drug-resistance to amphotericin B, further bolstering the use of this compound as

the most likely last resort treatment for fungal infections in the foreseeable future.

However, the use of amphotericin B is relatively

limited because it is currently only available as an IV-administered product and has documented history of severe toxicity (most notably

nephrotoxicity).

By utilizing our LNC Platform to nano-encapsulate amphotericin B, we have created an opportunity for the drug to be

administered orally with targeted delivery to infected cells and tissues, which we believe may have fewer side effects than the currently

available IV-formulations of amphotericin B, and potentially result in greater efficacy due to the ability to administer amphotericin

B safely for longer periods of time.

LNC delivery of amphotericin B changes the bio-distribution, resulting in a higher level of amphotericin B at the site of infection and

a lower level of free circulating drug.

By reducing the amount of circulating drug, our LNC Platform may reduce overall toxicity.

drug concentrations will be high only in target tissues due to the migratory nature of drug-carrying phagocytes to inflammatory regions.

Based upon data generated to date, we believe MAT2203 has the potential to offer improved safety and reduced toxicity, and, as a result,

we believe MAT2203 will be able to offer a categorically different and improved formulation that delivers orally administered amphotericin

B, directly to the target cell at the site of infection.

data from animal toxicity and human studies for MAT2203 indicate a substantial advantage over other amphotericin B formulations in observed

toxicities and side effects, which we believe is driven by two primary factors:

LNC is a solid crystal that does not significantly “leak” its drug content while circulating.

The crystal releases its

medication pay-load only when inside the target cells, and thus appears that the use of MAT2203 does not result in off-organ toxicities

normally seen in the kidneys when using current formulations of amphotericin B.

of this targeted delivery, we have been able to increase the therapeutic window on a mg/kg basis as compared to IV amphotericin B

formulations.

We have observed equivalent efficacy at lower doses as well as been able to use oral doses of up to 10x the highest

tolerable IV dose in animal model studies.

profile of MAT2203, which facilitates the oral, targeted, and non-toxic delivery of amphotericin B has the potential to fundamentally

change the treatment paradigm for IFIs, which are a rapidly growing global threat.

Increasing Problem of Fungal Pathogens

pathogens and infections are an increasing global public health concern.

IFIs are increasing globally due to advancements in the medical

management of critically ill and immunocompromised patients.

The emergence of drug-resistant IFIs has resulted in prolonged hospitalizations

and the increased use of expensive and often highly toxic second-line antifungal agents.

pathogens cause a wide variety of infections but there are only four currently available classes of systemic antifungal treatments (polyene,

azole, echinocandin, pyrimidine), and only two classes (azole, pyrimidine) are available in oral formulations.

Use of these antifungal

agents typically require a considerable degree of expertise to manage potential toxicities and complex drug-drug interactions in these

vulnerable patients and effective polyene and echinocandins require prolonged hospitalization for intravenous administration.

there is a critical unmet need for more effective, well-tolerated, and safe oral antifungal agents to treat patients with serious, life-threatening,

and often drug resistant IFIs.

World Health Organization (WHO) recently recognized IFIs to be a global public health concern.

In late 2022, the WHO released their Fungal

Priority Pathogen List which designates Aspergillus fumigates, Candida auris, and Candida albicans to be in the Critical Priority group

(i.e., highest perceived public health threat), Mucorales, Candida tropicalis, and Candida parapsilosis in the High Priority group, and

Coccidioides species in the Medium Priority group.

Aspergillus, Candida, Coccidioides, and Cryptococcus species are also qualified pathogens

that pose a serious and life-threatening risk and are on the qualified designation list according to 317.2 – CFR – Code of

Federal Regulations Title 21 – FDA.

believe that MAT2203 has the potential to become a best-in-class therapy for the treatment of IA and for other IFIs more broadly by offering

the following key potential benefits:

to treat resistant pathogens .

We believe that MAT2203 has the potential to prevent and treat fungal infections caused by drug-resistant

fungi, including those resistant to existing azoles and echinocandins, due to amphotericin B’s fungicidal (i.e., killing the

fungi) nature and potency against resistant strains and the potential for our LNC Platform to provide higher drug exposure directly

at the site of infection early during therapy.

an all-oral therapy.

The ability to step-down to an oral amphotericin B product early during treatment of an invasive fungal

infection will offer significant benefit to patients for whom there are only limited oral treatment options that carry significant

issues of safety, tolerability, and high propensity of resistance, as seen with the azole class of antifungals.

and less costly hospital stays and lower outpatient costs .

By providing physicians and patients with access to an orally available,

broad spectrum fungicidal agent in MAT2203, we believe that there is significant potential to reduce hospital costs, which account

for over 70% of the overall treatment cost of IFIs.

Development History and Plan

has demonstrated antifungal activity when administered orally in several animal models for Cryptococcus , Candida , and Aspergillus

infection [ Zarif et al, 2000 ;

Perlin, 2004 ;

Lu et al, 2019 ].

The efficacy in these animal models has been shown

to demonstrate comparable or superior antifungal activity compared to IV amphotericin B but with reduced toxicity.

in vivo efficacy of MAT2203 has been shown in multiple mouse models infected with Cryptococcus neoformans;

these studies

were conducted by Dr.

Peter Williamson at NIH [ Lu et al, 2019 ].

Multiple studies demonstrated the potential for MAT2203 to be

administered in combination with 5FC to provide an effective oral formulation for treatment of cryptococcal meningitis.

Using a 3-day

delayed model of murine cryptococcal meningoencephalitis and a large inoculum of a highly virulent strain of serotype A C.

MAT2203, administered in combination with 5FC, was found to have efficacy equivalent to administered amphotericin B deoxycholate with

5FC and superior to oral fluconazole without any observed toxicity.

The transport of fluorescent MAT2203 particles to the brain as well

as significant brain levels of amphotericin drug was demonstrated in treated mice, and immunological profiles were similar to those of

mice treated with conventional amphotericin B.

These studies suggest the potential for an efficacious oral formulation of a known fungicidal

drug against intrathecal cryptococcal disease.

MAT2203 therefore provides a promising therapeutic option for CM.

preclinical studies of MAT2203 have been conducted to investigate the treatment of other IFIs.

Oral MAT2203 was demonstrated to be effective

in multiple nonclinical studies .

In vitro studies have demonstrated that the MAT2203 LNC formulation did not have an impact on

the antifungal activity of amphotericin B.

Oral MAT2203 was demonstrated to be effective in several mouse models of systemic fungal infection

with Candida, Aspergillus, and Mucor.

In the Candida infection models in both immunocompromised and immunocompetent mice, the efficacy

of oral MAT2203 was comparable to intraperitoneal (IP) amphotericin B in terms of survival and reduction of tissue burden in target organs

of lung, liver, and kidneys of infected animals.

In the Aspergillus mouse models of infection, the efficacy of oral MAT2203 was comparable

to intraperitoneal amphotericin B in terms of survival, with dose-dependent reduction of fungal tissue burden.

Oral MAT2203 also demonstrated

in vivo efficacy in treating R.

delemar or M.

circinelloide s pulmonary infections in immunosuppressed mice and led

to a reduction in fungal spores in lung and brain comparable to results achieved with the liposomal intravenous amphotericin B.

Phase 2 Trial

a comprehensive preclinical data package, the NIH financially supported a grant application from the University of Minnesota to conduct

the EnACT Phase 2a/b trial in Uganda.

This study was initiated in October 2019 and explored the use of MAT2203 for both induction and

maintenance therapy in the treatment of cryptococcal meningitis, which is one of the most frequent and opportunistic infections in HIV

Given the high morbidity and mortality associated with CM in HIV patients, the clinical unmet need is very high with the global

burden estimated at 1 million cases annually.

consisted of two parts.

Part 1 of EnACT was conducted in HIV-positive patients with a history of cryptococcosis, evaluated ascending

oral doses of MAT2203, and identified a safe maximum tolerated dose for Part 2 of the trial.

2 of EnACT was a prospective, randomized, open-label sequential cohort clinical trial to investigate the safety, tolerability, and efficacy

of oral MAT2203 in 100 HIV-positive persons with cryptococcal meningitis compared to SOC.

The EnACT trial included a total of four cohorts

of patients, with the first two cohorts testing MAT2203 as early step-down therapy following initial treatment with IV amphotericin B

during the 14-day induction period, and the second two cohorts testing MAT2203 as potentially all oral therapy.

The induction period

for all patients in each cohort (active or control) is 14 days, followed by an additional four weeks of treatment (active or control)

during a consolidation/maintenance period.

Cohorts 1 and 3 were safety lead-ins to Cohorts 2 and 4, respectively, which were the key

efficacy cohorts for EnACT.

2 of EnACT was designed to assess the potential to treat CM infections with oral MAT2203 as a step-down treatment during the induction

phase of treatment immediately following only two days of IV amphotericin treatment, with continued treatment with MAT2203 for up to

six weeks during early maintenance treatment.

The primary efficacy endpoint for Part 2 of EnACT was early fungicidal activity (EFA) defined

as rate of clearance of Cryptococcus from the cerebrospinal fluid (CSF) (log 10 colony forming units [CFU]/mL/day) as measured

by serial quantitative fungal cultures over the first two weeks of treatment.

Cohort 2 of EnACT, we reported the following results:

Early Fungicidal Activity (EFA), Cerebrospinal Fluid (CSF) Sterilization, with No Evidence of Breakthrough Infections During Treatment

primary endpoint in EnACT was EFA, a measurement of cerebrospinal fluid fungal clearance.

EFA is a well-validated quantitative measure

of the efficacy of antifungal agents and is a key surrogate marker for survival.

EFAs of less than 0.20 log10 Cryptococcus colony

forming units (CFUs) per mL CSF per day are associated with significantly higher mortality and worse clinical outcomes 2 .

EFA measured above this threshold is clinically meaningful and represents robust fungal clearance.

In the second cohort of EnACT,

the mean EFA achieved with patients treated with MAT2203 was 0.38 log10 CFU/mL/day, with 95% confidence intervals (0.30 to 0.46)

significantly higher than the prespecified primary endpoint threshold of >0.20.

patients treated with MAT2203 who completed the induction phase achieved sterile CSF cultures during treatment (either during induction

or early consolidation phases).

was no evidence of breakthrough or relapsed cryptococcal infections observed in any of the patients during treatment with MAT2203

through 10 weeks.

survival was 95% in 40 patients randomized to receive MAT2203.

2020;71(5):e45-49

showed no evidence of renal toxicity or electrolyte abnormalities attributable to MAT2203, no major safety signals, and no use-limiting

tolerability issues, even with longer-term treatment with MAT2203 extended beyond induction into the consolidation phase, from week

Cohort 4 of EnACT, we reported the following results:

CSF yeast clearance rate exceeded the prespecified primary endpoint threshold target of >0.20, with a mean EFA achieved of 0.30

log 10 CFU/mL/day with 95% confidence intervals from 0.22 – 0.38.

participants with high baseline fungal burdens had noteworthy antifungal activity within the MAT2203 treatment arm, including one

patient with quantitative cryptococcal culture as high as 915,000 CFU/mL at the time of screening with effective clearance during

the induction period, a key demonstration of potent antifungal activity, even in the most challenging of cases.

40 patients receiving MAT2203 treatment, interim survival is currently 90%, while the survival rate at Week 2 was 95%.

patients had fewer Grade ≥3 Clinical Adverse Events (42%) vs.

SOC treatment (59%).

incidence of adverse events relating to kidney function and anemia were significantly lower for MAT2203 compared with the SOC treatment,

with no evidence of kidney toxicity seen with six weeks of oral MAT2203 treatment.

favorable safety and tolerability data seen in Cohort 4 support the use of oral MAT2203 for longer-term use, something not previously

feasible due to associated toxicities with currently available IV formulations of amphotericin B.

EnACT trial results were published in the Journal of Clinical Infectious Diseases in August 2023 as an Editor’s Choice manuscript.

Expanded/Compassionate

Use Access Program

completion of the EnACT Trial, we initiated our Expanded/Compassionate Use Access Program in 2022 to demonstrate that MAT2203 could have

a significant impact in treating patients with invasive fungal infections with limited or no treatment options, which are very similar

to the patients we believed we would be enrolling in a Phase 3 clinical trial.

patients to date have been enrolled in the Program at multiple healthcare institutions, including the University of Michigan, Johns Hopkins,

Nationwide Children’s Hospital, City of Hope, Vanderbilt University Medical Center, the National Institutes of Health, Children’s

Hospital of Philadelphia, Memorial Sloan Kettering Cancer Center, and the University of California, San Diego School of Medicine.

majority of enrolled patients are post-transplant or are undergoing treatment for underlying malignancies.

The infections being treated

with MAT2203 include a variety of micro-organisms (including Aspergillus , Mucorales species , Candidiasis , Fusarium

and suspected Coccidioides ) occurring at multiple sites of infection, including brain, bladder/colon, bone, lung, sinus, and

Most patients were receiving AmBisome® prior to enrollment but developed treatment-limiting nephrotoxicity and most also required

treatment for either azole-resistant organisms or had clinically failed azole therapy and had no other treatment options.

the 19 patients enrolled in the Program, 15 have available follow-up and 4 recently initiated or will soon commence treatment with MAT2203.

of the 15 patients had either complete clinical resolution or objective improvement in clinical markers of infection (including radiologic

and mycologic).

the 5 patients who completed their full individually specified course of treatment (ranging from 2 weeks to 1 year, depending on

the infection) - all have had complete clinical resolution with no relapses or recurrence of their infection.

additional patients have shown objective improvement in clinical markers and are continuing treatment with MAT2203 as planned.

of the 15 patients were unable to complete their individually specified course of treatment, although 2 saw significant clinical

improvement of their fungal infection and are included in the 12 overall successful cases.

patients transitioned to palliative care shortly after starting therapy with MAT2203 because of unanticipated progression of their

malignant disease.

patient discontinued therapy after two days due to underlying GI issues (i.e., Crohn’s disease).

patient passed away due to progression of their underlying disease approximately 8 weeks into therapy (but previously experienced

significant clinical improvement of their fungal infection).

patient discontinued MAT2203 treatment following 10 weeks of therapy due to underlying GI issues (long-standing nausea/vomiting),

but with improvement in their fungal infection.

all patients who experienced renal toxicity following treatment with AmBisome saw their renal function return to baseline after transitioning

to MAT2203 therapy and suffered no further renal side effects over the course of extended treatment with MAT2203.

plan to continue to evaluate opportunities to provide MAT2203 on a compassionate use basis for patients as we believe these are opportunities

to showcase the safety and efficacy of MAT2203 outside clinical trial settings which represent important additional patient data for

both FDA and prospective partners to review.

ORALTO Phase 3 Trial

February 2024, the Company announced that it has reached agreement with the FDA on the design of a the ORALTO trial, including consensus

on all critical elements of the registrational path for MAT2203.

is a Phase 3, randomized, multicenter, open-label, adjudicator-blinded study to evaluate the efficacy and safety of MAT2203 as an oral

step-down treatment following treatment with AmBisome (liposomal IV-amphotericin B) compared with the standard of care in patients with

invasive aspergillosis who have limited treatment options.

The primary efficacy endpoint is all-cause mortality at study day 42.

secondary objectives include:

demonstration

of superiority of oral-step down treatment with MAT2203 compared with AmBisome for treatment-related toxicities leading to changes

in treatment (i.e., dose adjustment/discontinuations or changes to treatment regimens);

survival benefit of MAT2203 using all-cause mortality at study day 84;

of the impact of MAT2203 on healthcare resource utilization and quality of life impact.

is expected to include approximately 216 adults with recently diagnosed probable or proven invasive aspergillosis who are being treated

with AmBisome due to their inability to receive an IV mold-active azole and with limited alternative treatment options.

to two days of initial treatment with AmBisome, eligible study participants will be entered into the study and randomized in a 2:1 ratio

to receive either oral MAT2203 or continued AmBisome treatment followed by standard of care.

study participants will receive up to 12 weeks of treatment starting from the first day of treatment with AmBisome.

It is anticipated

that all study participants will be hospitalized during the initial AmBisome treatment period.

After step-down to oral MAT2203, study

participants may be discharged from the hospital to continue treatment on an outpatient basis, as clinically appropriate.

independent Data Review Committee, who will be blinded to treatment, will adjudicate primary and secondary endpoints, including clinical,

radiological, and mycological responses.

Once approximately 75% of participants are enrolled, an independent Data Safety Monitoring Board

will review the overall pooled all-cause mortality rate in a blinded fashion to ensure that the sample size assumptions are reasonable

and that the study is adequately powered.

Should the pooled event differ substantially from expected levels, a sample size adjustment

can be made to the trial.

will be conducted at approximately 65 investigator sites in the U.S., Europe, South America, Middle East, and Asia Pacific.

is expected to commence in the second half of 2024 and is expected to require approximately 24 months.

are actively engaged in an ongoing partnership process for MAT2203, seeking one or more development and/or commercialization partners.

We will require either (i) the consummation of a partnership transaction, or (ii) raising additional capital, prior to commencing the

ORALTO trial.

on the data generated in Cohorts 2 and 4 of EnACT, data from our ongoing Expanded Access Program, and following our reaching agreement

with the FDA on the design of the ORALTO Phase 3 trial design, we believe we have a well-defined pathway to NDA submission for MAT2203

for an initial indication for the treatment of invasive aspergillosis in patients with limited treatment options.

Our overall development

strategy is to expand the indications for MAT2203 to include the treatment of other IFIs and even prophylaxis once a pharmacodynamic

bridge to IV amphotericin has been established through the planned ORALTO Trial.

Clinical Data Package

studies conducted to evaluate MAT2203 include two completed Phase 1 studies in healthy volunteers (Study CAM-102 and Study MB-70011),

and three Phase 2-like studies:

one completed study in patients with moderate to severe vulvovaginal candidiasis (VVC), one Phase 2a

study in patients with mucocutaneous candidiasis who are refractory or intolerant to standard non-IV therapies, and one Phase 2 study

in patients with cryptococcal meningitis.

of March 2024, MAT2203 has been administered to a total of 202 subjects in four clinical trials and through our Expanded/Compassionate

Use Access Program as follows:

healthy subjects (Studies CAM-102 [N=36] and MB-70011 [N=16])

patients with HIV and 101 patients with CM (EnACT study MB-70007),

patients with VVC (MB-70005)

patients with mucocutaneous (esophageal and oropharyngeal) candidiasis (MB-70004)

patients in our Expanded/Compassionate Use Access Program in patients

these studies, single doses of MAT2203 up to 2.0 g and repeated doses of MAT2203 up to 2.0 g/day and as long as 48 months have been safe

and well-tolerated.

Invasive Aspergillosis in Patients with Limited Treatment Options

aspergillosis (IA) is a serious and life-threatening invasive fungal infection that occurs primarily in severely immunocompromised patients

with hematological malignancies and in transplant recipients.

IA has been increasing globally due to advancements in the medical management

of these patients and has recently been recognized as a global public health concern.

In 2022, the World Health Organization released

their Fungal Priority Pathogen List that designated Aspergillus fumigatus , the most common cause of IA, to be in the Critical

Priority group (i.e., the highest perceived public health threat).

Aspergillus is also included in the FDA qualified designation

list of pathogens that pose a serious and life-threatening risk.

one-year mortality for patients with IA has been reported to be 41% in solid organ transplant recipients and up to 75% in stem cell transplant

Although outcomes have improved since the development of mold-active azoles, the use of these agents is often complicated

by treatment-limiting toxicities, drug-drug interactions, and the recent emergence of drug resistance.

Infectious Diseases Society of America (IDSA) Treatment Guidelines recommend that patients with IA receive treatment with a mold-active

azole for a minimum of 6 to 12 weeks, largely dependent on the degree and duration of immunosuppression, site of disease, and evidence

Although the mold-active azoles are generally effective, their use requires a considerable degree of expertise to manage

toxicities and drug-drug interactions which often limit duration of treatment.

caused by Aspergillus species that are resistant to mold-active azoles has been increasing globally due to the chronic use of

azoles and the widespread use of azole fungicides in agriculture.

This emerging resistance is particularly concerning because IA due

to azole-resistant Aspergillus is a life-threatening disease with a high mortality rate.

with hematological malignancies and transplant recipients often receive antifungal prophylaxis with a mold-active azole to prevent infection

during high-risk periods.

Recently, cases of breakthrough IA have been reported in patients receiving antifungal prophylaxis.

for these apparent failures of prophylaxis may be non-compliance, poor absorption, drug-drug interactions, or infection with a drug-resistant

Aspergillus species.

IDSA Treatment Guidelines recommend an intravenously administered amphotericin B, such as AmBisome, as an alternative for patients with

IA who are unable to receive treatment with a mold-active azole.

However, IV amphotericin B can cause nephrotoxicity and electrolyte

abnormalities which usually requires hospitalization for close monitoring and electrolyte supplementation.

Other complications of IV

amphotericin B include acute infusion reactions with dyspnea, hypoxia, chest and back pain, IV-site phlebitis, anemia, and hepatotoxicity.

As such, treatment with IV amphotericin B for more than a few weeks is generally not safe or practical.

There are no oral antifungals

available that will enable these patients to complete the recommended 6 to 12 weeks of treatment.

Accordingly, there is a critical unmet

medical need for effective and well-tolerated oral antifungal agents to treat these patients with IA.

elements of our strategy now include:

one or more partners to monetize the value of MAT2203 and raising additional non-dilutive capital through the licensing

or sale of our lead LNC Platform product candidate.

A partnership, whether through a license, sale or other transaction, would likely seek to advance MAT2203 into Phase 3 development as

quickly as possible, which could position a partner to commercialize MAT2203 upon approval and which could bring additional longer-term

value to the Company and its shareholders.

our cash resources while identifying and evaluating other strategic options for the Company, which could include the in-licensing

of one or more assets or seeking a merger partner for the Company.

Regulatory Designations

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overall global antifungal market was valued at approximately $15.8 billion in 2023 and is expected to reach approximately $20.5 billion

In 2021, the global invasive fungal infection market was valued at more than $7.21 billion and is expected to reach US $ 10.36

In 2021, the global invasive fungal infection market was valued at more than $7.2 billion and is expected to reach $10.4

billion in 2030.

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among Candida glabrata.

In 2022, the WHO issued a fungal priority pathogens list including cryptococcal neoformans, aspergillus

fumigatus and c.

albicans as critical priority for antifungal development due to the high unmet need.

We believe this underscores

the urgent need for new agents with demonstrated activity against resistant strains and that can be administered with significantly less

toxicity and the potential to discharge patients earlier to reduce hospital stays and associated costs.

Platform Expansion

addition to advancing MAT2203 into the ORALTO Phase 3 trial, we continue to expand the utilization of the LNC platform with small molecules