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Item 2. Management’s Discussion and Analysis

2025-05-15 compared with 2024-11-14 · 352 added, 335 removed, 79 unchanged (90% of the section changed)

Management’s Discussion and Analysis of Financial Condition and Results of Operations

In addition to historical information, the following Management’s Discussion and Analysis of Financial Condition and Results of

Operations contains forward-looking statements as defined under Section 21E of the Securities Exchange Act of 1934, as amended, and is subject to the safe harbor created therein for forward-looking statements.

Such statements include, but are

not limited to, statements concerning our anticipated operating results, research and development, clinical trials, regulatory proceedings, and financial resources, and can be identified by use of words such as, for example, “anticipate,”

“estimate,” “expect,” “project,” “intend,” “plan,” “believe” and “would,” “should,” “could” or “may.” All statements, other than statements of historical facts, included herein that address activities, events, or developments that the Company

expects or anticipates will or may occur in the future, are forward-looking statements, including statements regarding:

plans and expectations regarding clinical trials; plans and expectations regarding regulatory approvals; our strategy and

expectations for clinical development and commercialization of our products; potential strategic partnerships; expectations regarding the effectiveness of our products; plans for research and development and related costs; statements about

accounting assumptions and estimates; expectations regarding liquidity and the sufficiency of cash to fund currently planned operations through May 2025; our commitments and contingencies; and our market risk exposure.

Forward-looking

statements are based on current expectations, estimates and projections about the industry and markets in which Galectin Therapeutics operates, and management’s beliefs and assumptions.

These statements are not guarantees of future performance

and involve certain known and unknown risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements.

Such risks and uncertainties are related to and include, without limitation,

our early stage of development,

we have incurred significant operating losses since our inception and cannot assure you that we will generate revenue or profit,

our dependence on additional outside capital,

we may be unable to enter into strategic partnerships for the development, commercialization, manufacturing and distribution of our proposed product candidates,

uncertainties related to any litigation,

uncertainties related to our technology and clinical trials, including expected dates of availability of clinical data,

we may be unable to demonstrate the efficacy and safety of our developmental product candidates in human trials,

we may be unable to improve upon, protect and/or enforce our intellectual property,

we are subject to extensive and costly regulation by the U.S.

Food and Drug Administration (FDA) and by foreign regulatory authorities, which must approve our product candidates in development and could restrict

the sales and marketing and pricing of such products,

competition and stock price volatility in the biotechnology industry,

limited trading volume for our stock, concentration of ownership of our stock, and other risks detailed herein and from time to time in our SEC reports, and

the impact resulting from a pandemic or the reemergence of COVID-19, which delayed our clinical trial and development efforts, as well as the impact that such a pandemic has on the volatility of the capital

market and our ability to access the capital market and,

other risks detailed herein and from time to time in our SEC reports, including our Annual Report on Form 10-K filed with the SEC for the fiscal year ended December 31, 2023, and our subsequent SEC filings.

Discussion and Analysis of Financial Condition and Results of Operations

addition to historical information, the following Management’s Discussion and

Analysis of Financial Condition and Results of Operations contains

forward-looking statements as defined under Section 21E of the Securities

Exchange Act of 1934, as amended, and is subject to the safe harbor created

therein for forward-looking statements.

Such statements include, but are not

limited to, statements concerning our anticipated operating results, research

and development, clinical trials, regulatory proceedings, and financial

resources, and can be identified by use of words such as, for example,

“anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe” and

“would,” “should,” “could” or “may.” All statements, other than statements of

historical facts, included herein that address activities, events, or

developments that the Company expects or anticipates will or may occur in the

future, are forward-looking statements, including statements regarding:

and expectations regarding clinical

trials; plans and expectations regarding regulatory approvals; our strategy and

expectations for clinical development and commercialization of our products;

potential strategic partnerships; expectations regarding the effectiveness of

our products; plans for research and development and related costs; statements

about accounting assumptions and estimates; expectations regarding liquidity

and the sufficiency of cash to fund currently planned operations through August

31, 2025; our commitments and contingencies; and our market risk exposure.

Forward-looking statements are based on current expectations, estimates and

projections about the industry and markets in which Galectin Therapeutics

operates, and management’s beliefs and assumptions.

These statements are not

guarantees of future performance and involve certain known and unknown risks

and uncertainties that could cause actual results to differ materially from

those expressed or implied by such statements.

Such risks and uncertainties are

related to and include, without limitation,

early stage of development,

have incurred significant operating losses since our inception and cannot

assure you that we will generate revenue or profit,

dependence on additional outside capital,

may be unable to enter into strategic partnerships for the development,

commercialization, manufacturing and distribution of our proposed product

• uncertainties

related to any litigation,

• uncertainties

related to our technology and clinical trials, including expected dates of

availability of clinical data,

may be unable to demonstrate the efficacy and safety of our developmental

product candidates in human trials,

may be unable to improve upon, protect and/or enforce our intellectual

are subject to extensive and costly regulation by the U.S.

Food and Drug

Administration (FDA) and by foreign regulatory authorities, which must approve

our product candidates in development and could restrict the sales and

marketing and pricing of such products,

• competition

and stock price volatility in the biotechnology industry,

trading volume for our stock, concentration of ownership of our stock, and

other risks detailed herein and from time to time in our SEC reports, and

impact resulting from a pandemic or the reemergence of COVID-19, which delayed

our clinical trial and development efforts, as well as the impact that such a

pandemic has on the volatility of the capital market and our ability to access

the capital market and,

risks detailed herein and from time to time in our SEC reports, including our

Annual Report on Form 10-K filed with the SEC for the fiscal year ended

December 31, 2024, and our subsequent SEC filings.

The following discussion should be read in conjunction with the accompanying consolidated financial statements and notes thereto of Galectin Therapeutics appearing elsewhere herein.

We are a clinical stage biopharmaceutical company engaged in drug research and development to create new therapies for fibrotic disease, cancer and selected other diseases.

Our drug candidates are

based on our method of targeting galectin proteins, which are key mediators of biologic and pathologic functions.

We use naturally occurring, readily-available plant products as starting material in manufacturing processes to create proprietary,

patented complex carbohydrates with specific molecular weights and other pharmaceutical properties.

Our drug candidates are based on our method of targeting galectin proteins, which are key mediators of biologic and pathologic functions.

We use naturally occurring, readily-available plant products as starting material in manufacturing processes to create proprietary, patented complex carbohydrates with specific molecular weights and other pharmaceutical properties.

These complex carbohydrate molecules are appropriately formulated into acceptable pharmaceutical formulations.

Using these unique

carbohydrate-based candidate compounds that largely bind and inhibit galectin proteins, particularly galectin-3, we are undertaking the focused pursuit of therapies for indications where galectin proteins have a demonstrated role in the

pathogenesis of a given disease.

We focus on diseases with serious, life- threatening consequences and those where current treatment options are limited specifically in MASH (metabolic dysfunction-associated steatohepatitis) (formerly known as

non-alcoholic steatohepatitis or NASH) with cirrhosis and certain cancer indications.

Our strategy is to establish and implement clinical development programs that add value to our business in the shortest period of time possible and to seek

strategic partners when one of our programs becomes advanced and requires significant additional resources.

Our lead galectin-3 inhibitor is belapectin (GR-MD-02), which has been demonstrated in preclinical models to reverse liver fibrosis and cirrhosis and in clinical studies to decrease portal

hypertension and prevent its complication:

Using these unique carbohydrate-based candidate compounds that largely bind and inhibit galectin proteins, particularly galectin-3, we are undertaking the focused pursuit of therapies for indications where galectin proteins have a demonstrated role in the pathogenesis of a given disease.

We focus on diseases with serious, life-threatening consequences and those where current treatment options are limited specifically in NASH (non-alcoholic steatohepatitis) with cirrhosis and certain cancer indications.

Our strategy is to establish and implement clinical development programs that add value to our business in the shortest period of time possible and to seek strategic partners when one of our programs becomes advanced and requires significant additional resources.

Our lead galectin-3 inhibitor is belapectin (GR-MD-02), which has been demonstrated in preclinical models to reverse liver fibrosis and cirrhosis and in clinical studies to decrease portal hypertension and prevent its complication:

the development of esophageal varices.

Belapectin has the potential to treat many diseases due to galectin-3’s involvement in multiple key biological pathways such as fibrosis, immune cell function and

immunity, cell differentiation, cell growth, and apoptosis (cell death).

Belapectin has the potential to treat many diseases due to galectin-3’s involvement in multiple key biological pathways such as fibrosis, immune cell function and immunity, cell differentiation, cell growth, and apoptosis (cell death).

The importance of galectin-3 in the fibrotic process is supported by experimental evidence.

Animals with the galectin-3 gene “knocked-out” can no longer develop fibrosis in

response to experimental stimuli compared to animals with an intact galectin-3 gene.

Animals with the galectin-3 gene “knocked-out” can no longer develop fibrosis in response to experimental stimuli compared to animals with an intact galectin-3 gene.

We are using our galectin-3 inhibitor to treat advanced liver fibrosis and liver cirrhosis in NASH patients.

We have completed two Phase 1 clinical studies, a

Phase 2 clinical study in MASH patients with advanced fibrosis (NASH-FX) and a second Phase 2b clinical trial in NASH patients with compensated cirrhosis and portal hypertension (NASH-CX).

In February 2023, we completed randomizations totaling 357 patients in a large, global clinical trial, the NAVIGATE trial.

protocol was filed with the FDA on April 30, 2020, and originally provided for a seamless adaptively-designed Phase 2b/3 clinical study evaluating the safety and efficacy of our galectin-3 inhibitor, belapectin, for the prevention of esophageal

varices in patients with MASH cirrhosis (Further details are available at www.clinicaltrials.gov under study NCT04365868.

In September 2020, the Company received a letter from the FDA providing comments, asking questions and providing guidance on

various aspects of the ongoing NAVIGATE trial.

We have completed two Phase 1 clinical studies, a Phase 2 clinical study in NASH patients with advanced fibrosis (NASH-FX) and a second Phase 2b clinical trial in NASH patients with compensated cirrhosis and portal hypertension (NASH-CX).

In February 2023, we completed randomizations totaling 357 patients in a large, global Phase 2b/3 clinical trial, the NAVIGATE trial.

Our study protocol was filed with the FDA on April 30, 2020, for a seamless adaptively-designed Phase 2b/3 clinical study evaluating the safety and efficacy of our galectin-3 inhibitor, belapectin, for the prevention of esophageal varices in patients with non-alcoholic steatohepatitis (NASH) cirrhosis Further details are available at www.clinicaltrials.gov under study NCT04365868.

The information contained therein is not incorporated herein by reference.

In September 2020, the Company received a letter from the FDA providing comments, asking questions and providing guidance on various aspects of the ongoing NAVIGATE trial.

These comments were addressed, and the study proceeded accordingly.

Based on more recent FDA feedback, the Company decided to analyze the stage 1 portion of the NAVIGATE study as a stand-alone

clinical trial and currently does not expect to conduct the originally planned stage 2 portion of study as was initially designed.

Impairment” has been filed with the FDA to examine the effects of the drug in subjects with normal hepatic function and subjects with varying degrees of hepatic impairment (study details are listed under study NCT04332432 on www.clinicaltrials.gov );

Based on feedback from the U.S.

Food and Drug Administration (FDA), the Company decided to analyze stage 1 of the NAVIGATE clinical trial results as a stand-alone trial.

Therefore, the decision was made to present full top-line efficacy and safety results, following last patient last visit and database lock which occurred in fall 2024.

In December 2024, we presented top-line results of the NAVIGATE clinical trial.

In the intent-to-treat (ITT) population (N=355), while the incidence of varices was 43.2% reduced in the belapectin 2 mg/kg dose group vs placebo, the composite endpoint did not reach statistical significance.

The per-protocol population (PPP) was pre-defined as subjects who completed 18 months of therapy with upper endoscopy performed at both baseline and 18 months.

In the PPP (n=287), the incidence of varices was reduced by 49.3% (compared to the targeted 52.5% reduction) in the belapectin 2 mg/kg dose group (p-value < 0.05).

The Company further analyzed the two thirds of the completer patients in the NAVIGATE trial enrolled in the U.S.

The incidence of varices in this population was significantly reduced by 68.1% (p=0.02) in patients treated with belapectin 2 mg (4 out of 60) vs placebo (13 out of 62) in the U.S.

While all three cohorts of patients in the U.S.

had a higher percentage use of GLP-1 and statins than the rest of the world, the belapectin cohorts performed much better than placebo in the U.S.

The Company continues to analyze trial data and expects to report additional information on specific biomarkers in the second quarter of 2025.

As in prior trials, the safety profile of belapectin remains highly encouraging with incidence of adverse events and serious adverse events comparable across the three cohorts.

Rates of discontinuation, adverse events (AEs), and serious adverse events (SAEs) were comparable to placebo, with no drug-related SAEs reported in the NAVIGATE trial.

The Company continues to analyze data from approximately 55 patients that completed 36 months of treatment prior to the ending of the trial in February 2025.

While data from this group would not change the results of the NAVIGATE clinical trial for patients completing 18 months of treatment, the Company believes that any encouraging results from this group of patients may draw interest from potential strategic partners.

Additionally, a study protocol entitled “A Single-dose, Open-label, Pharmacokinetic Study of Belapectin (GR-MD-02) in Subjects With Normal Hepatic Function and Subjects With Varying Degrees of Hepatic Impairment” has been filed with the FDA to examine the effects of the drug in subjects with normal hepatic function and subjects with varying degrees of hepatic impairment (study details are listed under study NCT04332432 on www.clinicaltrials.gov );

this study became fully enrolled in February 2022 and favorable results were reported in 2023.

The information contained therein is not incorporated herein by reference.

We endeavor to leverage our scientific and product development expertise as well as established relationships with outside sources to achieve cost-effective and efficient drug development.

outside sources, amongst others, provide us with expertise in preclinical models, pharmaceutical development, toxicology, clinical trial operations, pharmaceutical manufacturing, including physical and chemical drug characterization, and

commercial development.

We also have established through our majority-owned joint venture subsidiary, Galectin Sciences LLC, a discovery program developing small molecules that inhibit galectin-3 and may afford alternative drug delivery (e.g.,

oral) and as a result expand the potential uses of galectin-3 inhibitor beyond belapectin.

These outside sources, amongst others, provide us with expertise in preclinical models, pharmaceutical development, toxicology, clinical trial operations, pharmaceutical manufacturing, including physical and chemical drug characterization, and commercial development.

Three chemical series of composition of matter patents have been filed.

We are also pursuing a development pathway to clinical enhancement and commercialization for our lead compounds in immuno-oncology following our previous successful collaboration with Providence

Portland Cancer Center.

We are also pursuing a development pathway to clinical enhancement and commercialization for our lead compounds in immuno-oncology following our previous successful collaboration with Providence Portland Cancer Center.

In 2022, we filed a new IND with FDA for advanced or metastatic head and neck cancer using belapectin in combination with a checkpoint (PD-1) inhibitor and received a Study May Proceed letter.

The proposed phase 2 trial

commencement is dependent on timing of financing.

The proposed phase 2 trial commencement is dependent on timing of financing.

All of our proposed products are presently in development, including pre-clinical and clinical trials.

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Galectins are a class of proteins that are made by many cells in the body, but predominantly in cells of the immune system.

As a group, these proteins are able to bind to sugar molecules that are

attached to other proteins, called glycoproteins that are responsible for various functions within the body, most notably inflammation and fibrosis.

Galectins, in particular galectin-3, act as a molecular glue, bringing together molecules that

have sugars on them.

As a group, these proteins are able to bind to sugar molecules that are attached to other proteins, called glycoproteins that are responsible for various functions within the body, most notably inflammation and fibrosis.

Galectins, in particular galectin-3, act as a molecular glue, bringing together molecules that have sugars on them.

Galectin-3, is known to be markedly increased in a number of significant diseases including inflammatory diseases leading to organs scarring (e.g.

liver, lung, kidney, and heart) and cancers.

The increase in galectin-3, by

creating the so-called galectin-3 fibrosome, promotes the progression of multiple diseases.

The increase in galectin-3, by creating the so-called galectin-3 fibrosome, promotes the progression of multiple diseases.

Published data substantiating the importance of galectin-3 in the fibrotic process arises from gene knockout experiments in animal studies.

For instance,

mice genetically altered to eliminate the galectin-3 gene, and thus unable to produce galectin-3, do not develop liver fibrosis in response to toxic insult to the liver.

We have one new proprietary chemical entity (NCE) in development, belapectin, which has shown promise in preclinical and clinical studies for the treatment of liver fibrosis, severe skin disease, and

cancer (melanoma and head and neck squamous cell carcinoma).

For instance, mice genetically altered to eliminate the galectin-3 gene, and thus unable to produce galectin-3, do not develop liver fibrosis in response to toxic insult to the liver.

We have one new proprietary chemical entity (NCE) in development, belapectin, which has shown promise in preclinical and clinical studies for the treatment of liver fibrosis, severe skin disease, and cancer (melanoma and head and neck squamous cell carcinoma).

Currently, we are focusing on development of belapectin for the treatment of NASH cirrhosis and head and neck cancer.

Belapectin is a proprietary, patented compound derived from

natural, plant-based, starting materials, which following chemical processing, exhibits the properties of binding to and inhibiting galectin-3.

Belapectin is a proprietary, patented compound derived from natural, plant-based, starting materials, which following chemical processing, exhibits the properties of binding to and inhibiting galectin-3.

Our product pipeline is shown below:

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The Phase 2 NASH FX trial was conducted in patients with advanced fibrosis but not cirrhosis.

Its principal purpose was to evaluate various

imaging modalities.

Its principal purpose was to evaluate various imaging modalities.

The NASH FX trial top line data was reported in September 2016 and published in Alimentary Pharmacology and Therapeutics in 2016.

The Phase 2 NASH CX trial was conducted in patients with compensated cirrhosis and portal hypertension.

The NASH CX trial top line data was

reported in December 2017 and was published in Gastroenterology in 2020.

The NASH CX trial top line data was reported in December 2017 and was published in Gastroenterology in 2020.

NASH NAVIGATE

Following FDA feedback, the NAVIGATE trial is an adaptive Phase 2b/3 trial for the prevention of esophageal varices in MASH patients with

compensated cirrhosis and clinical signs of portal hypertension.

A stage 1 interim efficacy analysis originally was planned to confirm previous Phase 2 data, select an optimal dose and reaffirm the risk/benefit of belapectin.

required, the stage 2 end of study analysis will evaluate the development of esophageal varices as the same primary outcome of efficacy and a composite clinical endpoint including progression to varices requiring treatment as a key

secondary outcome of efficacy (www.clinicaltrials.gov NCT04365868).

However, following FDA feedback, the Company decided to analyze the stage 1 portion of the NAVIGATE study as a stand-alone clinical trial and the Company currently

does not expect to conduct the originally planned stage 2 portion of study as was initially designed.

The final patient was randomized in February 2023 and the top line efficacy and safety results are expected in December 2024.

Following FDA feedback, the NAVIGATE trial was for the prevention of esophageal varices in NASH patients with compensated cirrhosis and clinical signs of portal hypertension..

The final patient was randomized in February 2023 and top-line results were presented in December 2024

Phase 1 study:

hepatic insufficiency

A hepatic impairment study was conducted in subjects with normal hepatic function and subjects with varying degrees of hepatic impairment

(www.clinicaltrials.gov NCT04332432) and began enrolling patients in the second quarter of 2020.

A hepatic impairment study was conducted in subjects with normal hepatic function and subjects with varying degrees of hepatic impairment (www.clinicaltrials.gov NCT04332432) and began enrolling patients in the second quarter of 2020.

The study completed enrollment in February 2022 and favorable results were presented in 2023.

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A Phase 1B study began in Q-1 2016.

Early data was reported in February 2017 and additional data were

reported in September 2018.

Early data was reported in February 2017 and additional data were reported in September 2018.

Data from an extension trial was reported in July 2021 for additional melanoma and HNSCC patients which provided a rational basis for additional trials which the Company is exploring.

In the third quarter of

2022, the Company announced its IND application for belapectin in combination with a checkpoint inhibitor for the treatment of HNSCC was filed and a Study May Proceed letter was received from FDA.

The Company is reviewing options for

financing this trial which will determine when such trial could commence.

Liver cirrhosis.

Belapectin is our lead product candidate for treatment of compensated MASH cirrhosis in patients with portal hypertension.

Our preclinical data show that belapectin has a significant therapeutic effect on liver fibrosis as shown in several relevant animal models.

In addition, in MASH animal models, belapectin has been shown to reduce

liver fat, inflammation, portal pressure, and ballooning degeneration (death of liver cells).

Therefore, we chose belapectin as the lead candidate in a development program targeted initially at fibrotic liver disease associated with MASH.

January 2013, an Investigational New Drug (“IND”) was submitted to the FDA with the goal of initiating a Phase 1 study in patients with MASH and advanced liver fibrosis to evaluate the safety of belapectin and pharmacodynamics biomarkers of

On March 1, 2013, the FDA indicated we could proceed with a US Phase 1 clinical trial for belapectin with a development program aimed at obtaining support for a proposed indication of belapectin for treatment of MASH with advanced

The Phase 1 trial was completed and demonstrated that belapectin up to 8 mg/kg Lean Body Mass (LBM), i.v.

In the third quarter of 2022, the Company announced its IND application for belapectin in combination with a checkpoint inhibitor for the treatment of HNSCC was filed and a Study May Proceed letter was received from FDA.

The Company is reviewing options for financing this trial which will determine when such trial could commence.

Belapectin is our lead product candidate for

treatment of compensated NASH cirrhosis in patients with portal hypertension.

Our preclinical data show that belapectin has a significant therapeutic effect

on liver fibrosis as shown in several relevant animal models.

In addition, in

NASH animal models, belapectin has been shown to reduce liver fat,

inflammation, portal pressure, and ballooning degeneration (death of liver

Therefore, we chose belapectin as the lead candidate in a development

program targeted initially at fibrotic liver disease associated with

non-alcoholic steatohepatitis (NASH).

In January 2013, an Investigational New

Drug (“IND”) was submitted to the FDA with the goal of initiating a Phase 1

study in patients with NASH and advanced liver fibrosis to evaluate the safety

of belapectin and pharmacodynamics biomarkers of disease.

On March 1, 2013, the

FDA indicated we could proceed with a US Phase 1 clinical trial for belapectin

with a development program aimed at obtaining support for a proposed indication

of belapectin for treatment of NASH with advanced fibrosis.

The Phase 1 trial

was completed and demonstrated that belapectin up to 8 mg/kg Lean Body Mass

was safe and well tolerated.

Additionally, an open label drug-drug phase 1 interaction study was completed in healthy volunteers during the second quarter of 2015 with belapectin and it showed that with 8 mg/kg LBM dose of

belapectin and 2 mg/kg LBM dose of midazolam there was no drug-drug interaction, and no serious adverse events or drug-related adverse events were observed.

The secondary objective was to assess the safety and tolerability of belapectin when

administered concomitantly with midazolam.

Additionally, an open label drug-drug phase 1 interaction study was completed in healthy volunteers during the second quarter of 2015 with belapectin and it showed that with 8 mg/kg LBM dose of belapectin and 2 mg/kg LBM dose of midazolam there was no drug-drug interaction, and no serious adverse events or drug-related adverse events were observed.

The secondary objective was to assess the safety and tolerability of belapectin when administered concomitantly with midazolam.

Our Phase 2 program in fibrotic disease consisted of two separate human clinical trials.

The main clinical trial was the Phase 2b NASH-CX study for one year for patients with MASH with compensated

cirrhosis and portal hypertension, which began enrolling patients in June 2015.

This study was a randomized, placebo-controlled, double-blind, parallel-group Phase 2b trial to evaluate the safety and efficacy of belapectin for treatment of liver

fibrosis and resultant portal hypertension in MASH patients with compensated cirrhosis.

A smaller, exploratory NASH-FX trial was conducted to explore potential use of various non-invasive imaging techniques in MASH patients with advanced fibrosis

but not cirrhosis.

NASH-FX Trial :

The NASH-FX trial was a Phase 2a pilot trial for patients with MASH and advanced fibrosis that explored use of three non-invasive imaging

The main clinical trial was the Phase 2b NASH-CX study for one year for patients with NASH with compensated cirrhosis and portal hypertension, which began enrolling patients in June 2015.

This study was a randomized, placebo-controlled, double-blind, parallel-group Phase 2b trial to evaluate the safety and efficacy of belapectin for treatment of liver fibrosis and resultant portal hypertension in NASH patients with compensated cirrhosis.

A smaller, exploratory NASH-FX trial was conducted to explore potential use of various non-invasive imaging techniques in NASH patients with advanced fibrosis but not cirrhosis.

The NASH-FX trial was a Phase 2a pilot trial for patients with

NASH and advanced fibrosis that explored use of three non-invasive imaging

technologies.

It was a short, single site, four-month trial in 30 NASH patients with advanced fibrosis (F3) randomized 1:1 to either 9 bi-weekly doses of 8 mg/kg LBM of belapectin or placebo.

The trial did not meet its primary endpoint as

measured using multi-parametric magnetic resonance imaging (LiverMultiScan ® , Perspectum Diagnostics).

The trial also did not meet secondary endpoints that measure liver stiffness as a surrogate for fibrosis using, magnetic

resonance-elastography and FibroScan ® score.

With a four-month treatment period and a small number of patients per arm the study was not powered to demonstrate

efficacy results in established advanced liver fibrosis.

In the trial however, belapectin was found to be safe and well tolerated with no serious adverse events and showing evidence of a pharmacodynamic effect.

These results provided support for

further development in MASH.

NASH-CX Trial :

The NASH-CX trial was a larger multi-center clinical trial that explored the use of belapectin for the treatment of patients with

well-compensated MASH cirrhosis and portal hypertension.

Enrollment was completed in September 2016, and a total of 162 patients at 36 sites in the United States were randomized to receive either 2 mg/kg LBM of belapectin, 8 mg/kg LBM of

belapectin or placebo.

Approximately 50% of patients at baseline had esophageal varices (a complication of portal hypertension).

The primary endpoint was a reduction in hepatic venous pressure gradient (HVPG), a hemodynamic measure that estimates

portal hypertension.

Patients received an infusion of belapectin or placebo every other week for one year and were evaluated to determine the change in HVPG as compared with placebo.

Secondary or exploratory endpoints included evaluation of

fibrosis on liver biopsy, measurement of liver stiffness (FibroScan) and assessment of liver metabolism ( 13 C-methacetin breath test).

Top line data readout was

reported in December 2017.

The study demonstrated a favorable safety profile and clinically meaningful efficacy results in patients without esophageal varices at baseline as demonstrated by a decrease in portal pressure associated with the

prevention of development of varices when compared to placebo.

In the total patient population, the primary endpoint HVPG showed a trend toward benefit with belapectin treatment, but the difference from placebo was not statistically

It was a short, single site, four-month trial in 30 NASH patients

with advanced fibrosis (F3) randomized 1:1 to either 9 bi-weekly doses of 8

mg/kg LBM of belapectin or placebo.

The trial did not meet its primary endpoint

as measured using multi-parametric magnetic resonance imaging (LiverMultiScan (R) ,

Perspectum Diagnostics).

The trial also did not meet secondary endpoints that

measure liver stiffness as a surrogate for fibrosis using, magnetic

resonance-elastography and FibroScan ®

With a four-month treatment period and a small number of patients per

arm the study was not powered to demonstrate efficacy results in established

advanced liver fibrosis.

In the trial however, belapectin was found to be safe

and well tolerated with no serious adverse events and showing evidence of a

pharmacodynamic effect.

These results provided support for further development

The NASH-CX trial was a larger multi-center clinical trial that

explored the use of belapectin for the treatment of patients with

well-compensated NASH cirrhosis and portal hypertension.

Enrollment was

completed in September 2016, and a total of 162 patients at 36 sites in the

United States were randomized to receive either 2 mg/kg LBM of belapectin, 8

mg/kg LBM of belapectin or placebo.

Approximately 50% of patients at baseline

had esophageal varices (a complication of portal hypertension).

endpoint was a reduction in hepatic venous pressure gradient (HVPG), a

hemodynamic measure that estimates portal hypertension.

Patients received an

infusion of belapectin or placebo every other week for one year and were

evaluated to determine the change in HVPG as compared with placebo.

or exploratory endpoints included evaluation of fibrosis on liver biopsy,

measurement of liver stiffness (FibroScan) and assessment of liver metabolism ( 13 C-methacetin

breath test).

Top line data readout was reported in December 2017.

demonstrated a favorable safety profile and clinically meaningful efficacy

results in patients without esophageal varices at baseline as demonstrated by a

decrease in portal pressure associated with the prevention of development of

varices when compared to placebo.

In the total patient population, the primary endpoint HVPG showed a trend toward benefit with belapectin treatment, but the difference from placebo was not statistically significant.

The mean change in HVPG of placebo from baseline to week 54 was 0.3 mm Hg.

The mean change in HVPG from baseline was -0.37 and -0.42 for the 2 mg/kg LBM dose and 8 mg/kg LBM dose of belapectin, respectively.

In those MASH cirrhosis patients with portal hypertension who have not yet developed esophageal varices at baseline (about 50% of the total population), there was a statistically significant effect of

the 2 mg/kg LBM dose of belapectin on the absolute change in HVPG (-1.08 mm Hg, p<0.01).

In those NASH cirrhosis patients with portal hypertension who have not yet developed esophageal varices at baseline (about 50% of the total population), there was a statistically significant effect of the 2 mg/kg LBM dose of belapectin on the absolute change in HVPG (-1.08 mm Hg, p<0.01).

The effect of the 8 mg/Kg LBM dose of belapectin on absolute or percent change in HVPG from baseline to week 54 was not significant.

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those with an equal to or greater than 2 mm Hg decrease in HVPG from baseline or those with an equal to or greater than 2 mm Hg and a greater than or equal to 20% decrease in HVPG from baseline.

In both cases, the change observed in the

belapectin 2 mg/kg LBM group was statistically significant (p<0.01) while that of the 8 mg/kg LBM group was not.

Over the 54-week treatment period, in patients without varices at baseline there were also a statistically significantly fewer new varices that developed in the belapectin treatment groups (0% and 4%

in the 2 mg/kg LBM and the 8 mg/kg LBM, respectively) vs placebo (18%).

In both cases, the change observed in the belapectin 2 mg/kg LBM group was statistically significant (p<0.01) while that of the 8 mg/kg LBM group was not.

Over the 54-week treatment period, in patients without varices at baseline there were also a statistically significantly fewer new varices that developed in the belapectin treatment groups (0% and 4% in the 2 mg/kg LBM and the 8 mg/kg LBM, respectively) vs placebo (18%).

This meant that the decrease seen in portal pressure was associated with a decreased incidence of esophageal varices.

The results were noticeable in the belapectin 2 mg/Kg

LBM group as statistical significance against placebo was achieved for both parameters.

As esophageal varices can lead to hemorrhagic complication, which can be fatal, and are a severe complication of liver cirrhosis, we believe the prevention of

esophageal varices may represent a clinically relevant measure of clinical efficacy in patients with NASH cirrhosis.

The results were noticeable in the belapectin 2 mg/Kg LBM group as statistical significance against placebo was achieved for both parameters.

As esophageal varices can lead to hemorrhagic complication, which can be fatal, and are a severe complication of liver cirrhosis, we believe the prevention of esophageal varices may represent a clinically relevant measure of clinical efficacy in patients with NASH cirrhosis.

The major conclusions from the NASH-CX trial results were that:

(i) belapectin had a statistically significant and clinically meaningful effect in improving HVPG vs placebo in patients with MASH

cirrhosis who did not have esophageal varices at baseline, (ii) Belapectin in the total patient population was associated with a statistically significant improvement in hepatocyte ballooning (i.e.

cell death), (iii) There was a statistically

significant reduction (p=0.02) in the development of new esophageal varices in drug-treated patients compared to placebo.

We believe that the prevention of esophageal varices is a clinically relevant endpoint related to patient outcomes, (iv)

While there was a drug effect in both the 2 mg/kg LBM and 8 mg/kg LBM groups on the development of varices and liver biopsy there was a consistently greater and statistically significant effect of the 2 mg/kg LBM dose of belapectin, (v)

belapectin appears to be safe and well tolerated in this one year clinical trial, a feature that is of prime importance for a cirrhotic population and (vi) This is the first large, randomized clinical trial to demonstrate a clinically meaningful

improvement in portal hypertension in patients with compensated MASH cirrhosis who have not yet developed esophageal varices.

(i) belapectin had a statistically significant and clinically meaningful effect in improving HVPG vs placebo in patients with NASH cirrhosis who did not have esophageal varices at baseline, (ii) Belapectin in the total patient population was associated with a statistically significant improvement in hepatocyte ballooning (i.e.

cell death), (iii) There was a statistically significant reduction (p=0.02) in the development of new esophageal varices in drug-treated patients compared to placebo.

We believe that the prevention of esophageal varices is a clinically relevant endpoint related to patient outcomes, (iv) While there was a drug effect in both the 2 mg/kg LBM and 8 mg/kg LBM groups on the development of varices and liver biopsy there was a consistently greater and statistically significant effect of the 2 mg/kg LBM dose of belapectin, (v) belapectin appears to be safe and well tolerated in this one year clinical trial, a feature that is of prime importance for a cirrhotic population and (vi) This is the first large, randomized clinical trial to demonstrate a clinically meaningful improvement in portal hypertension in patients with compensated NASH cirrhosis who have not yet developed esophageal varices.

Further information and details on the NASH-CX results is available in public presentations posted to our website and filed with the SEC and in a peer reviewed publication in Gastroenterology 2020;158:1334–1345.

NASH NAVIGATE Trial :

Building on the experience of the NASH-CX trial, the NAVIGATE Trial is a seamless adaptively-designed Phase 2b/3 clinical study

evaluating the safety and efficacy of our galectin-3 inhibitor, belapectin, for the prevention of esophageal varices in patient with MASH cirrhosis.

The major features of this innovative Phase 2b/3 study design are:

i) In patients with NASH

cirrhosis and clinical signs of portal hypertension but without esophageal varices at baseline, evaluated by an esophago-gastro-duodeno endoscopy, this trial will assess the effect of belapectin on the incidence of new varices (the primary

endpoint) – as well as assessing the effect of belapectin on the incidence of additional clinically significant cirrhosis-related outcomes (a key secondary efficacy endpoint), (ii) The study targets MASH patients with a clearly identified unmet

medical need:

patients with compensated cirrhosis who have clinical signs of portal hypertension and, thus, are at risk of developing esophageal varices, a potentially life-threatening complication of cirrhosis (bleeding varices are a cause of

NAVIGATE Trial:

Building on the experience of the NASH-CX trial,

the NAVIGATE Trial was designed as a seamless adaptively-designed Phase 2b/3

clinical study evaluating the safety and efficacy of our galectin-3 inhibitor,

belapectin, for the prevention of esophageal varices in patient with

non-alcoholic steatohepatitis (NASH) cirrhosis.

The major features of this

innovative Phase 2b/3 study design are:

i) In patients with NASH cirrhosis and

clinical signs of portal hypertension but without esophageal varices at

baseline, evaluated by an esophago-gastro-duodeno endoscopy, this trial will

assess the effect of belapectin on the incidence of new varices (the primary endpoint) – as well as assessing

the effect of belapectin on the incidence of additional clinically significant

cirrhosis-related outcomes (a key secondary efficacy endpoint), (ii) The study

targets NASH patients with a clearly identified unmet medical need:

with compensated cirrhosis who have clinical signs of portal hypertension and,

thus, are at risk of developing esophageal varices, a potentially

life-threatening complication of cirrhosis (bleeding varices are a cause of

death in about one-third of cirrhotic patients).

There is currently no approved treatment for preventing varices in these patients.

In addition, the development of esophageal varices reflects the progression of hepatic cirrhosis and thus portends

the development of other cirrhosis complications such as ascites, hepatic encephalopathy, and liver failure, and (iii) During the first 18 months, two belapectin dose levels (2 mg/kg LBM and 4 mg/kg LBM) will be compared to placebo (phase 2b).

Then, at the interim analysis (IA), assuming the study continues to the next stage, the best belapectin dose will be selected, based on efficacy and safety, for continued evaluation (Phase 3).

The belapectin doses selected for the phase 2b/3 were

based on the analysis of the NASH-CX trial.

Prior belapectin clinical studies have also indicated the good tolerance and safety profile of belapectin with doses of up to 8 mg/kg LBM for up to 52 weeks, an important feature to inform the future

risk benefit analysis in patients with MASH cirrhosis.

Originally, an interim analysis (IA) of efficacy and safety data will be conducted after all planned subjects in stage 1 Phase 2b

component have completed at least 78 weeks (18 months) of treatment and a second esophago-gastro-duodeno endoscopic assessment has been performed.

The purpose of the IA is to allow potential seamless adaptive modifications of the phase 3 stage of

the study, including:

(1) the selection of the optimal dose of belapectin for Phase 3, (2) the re-estimation of the study sample size, (3) the modification of the randomization ratio in favor of the active treatment, (4) and/or termination of the

study for overwhelming efficacy or for futility.

However, following FDA feedback, the Company decided to analyze the stage 1 portion of the NAVIGATE study as a stand-alone clinical

trial and the Company currently does not expect to conduct the originally planned stage 2 portion of study as it was initially designed.

The topline efficacy and safety results are expected late in December 2024.

The trial design also included a blinded sample size re-estimation (“SSR”) during the Phase 2b, prior to the IA, to allow for

potential sample size readjustment.

The SSR was conducted when 50% of the patients completed 18 months of therapy.

The study design also minimizes invasive testing requirements, such as the measurement of HVPG or repeated liver biopsies, which we

believe are particularly risky in patients with portal hypertension and facilitated enrollment of patients and should facilitate their retention.

It also originally provided for a seamless transition of patients from the Phase 2b stage into the

phase 3 stage, including the potential addition of new patients.

The trial design introduces the notion of esophageal varices prevention as a primary pivotal outcome previously discussed with FDA.

We believe that these adaptations taken together are innovative and optimize conduct of the NAVIGATE trial with a clinically relevant primary outcome giving belapectin the best opportunity to show a

positive therapeutic effect to address an unmet medical need.

As a testimony of this innovation, the NAVIGATE trial design was presented to the hepatology community and featured during the meeting of the American Association for the Study of

Liver Diseases, in November 2021.

If the IA results of the NAVIGATE trial are compelling, there could be the potential for accelerated FDA approval pathway and/or partnership opportunity with a pharmaceutical company.

In this trial, as proposed in the protocol, secondary endpoints include a composite clinical outcomes endpoint, including varices requiring treatment (development of large varices or varices with a

red wale), decompensating events, all-cause mortality, MELD score increase, liver transplant.

Also, MASH non-invasive biomarkers will be evaluated.

To target a population at risk of developing esophageal varices, patient selection was based on

clinical signs of portal hypertension, including, but not limited to, a low platelet count, an increased spleen size, an increased liver stiffness, and/or evidence of abdominal collaterals circulation.

The focus and goal of the therapeutic program is to stop the progression of and/or reverse portal hypertension and thereby prevent the development of varices, potentially one of

the most life-threatening complications of cirrhosis.

Based on the results of the NASH-CX trial and subject to confirmation in later stage clinical trials, we believe that this goal is achievable in a significant portion of the MASH cirrhosis

patient population i.e.

those MASH cirrhosis patients with clinical signs of portal hypertension for whom, currently, apart from a liver transplantation, no specific liver targeted, treatments are available.

There is currently no approved

treatment for preventing varices in these patients.

In addition, the

development of esophageal varices reflects the progression of hepatic cirrhosis

and thus portends the development of other cirrhosis complications such as

ascites, hepatic encephalopathy, and liver failure, and (iii) During the first

18 months, two belapectin dose levels (2 mg/kg LBM and 4 mg/kg LBM) will be

compared to placebo (phase 2b).

Based on feedback from the U.S.

Food and Drug Administration (FDA), the Company has decided to analyze stage 1 of the NAVIGATE clinical trial results as a stand-alone trial.

Therefore, a decision was made to present full top-line efficacy and safety results, following last patient last visit and database lock which occurred in fall 2024.

In December 2024, we presented top-line results of the NAVIGATE clinical trial.

The per-protocol population (PPP) was pre-defined as subjects who completed 18 months of therapy with upper endoscopy performed at both baseline and 18 months.

In the PPP (n=287), the incidence of varices was reduced by 49.3% (compared to the targeted 52.5% reduction) in the belapectin 2 mg/kg dose group (p-value < 0.05).

The Company further analyzed the two thirds of the completer patients in the NAVIGATE trial enrolled in the U.S.

The incidence of varices in this population was significantly reduced by 68.1% (p=0.02) in patients treated with belapectin 2 mg (4 out of 60) vs placebo (13 out of 62) in the U.S.

While all three cohorts of patients in the U.S.

had a higher percentage use of GLP-1 and statins than the rest of the world, the belapectin cohorts performed much better than placebo in the U.S.

The Company continues to analyze trial data and expects to report additional information on specific biomarkers in the second quarter of 2025.

As in prior trials, the safety profile of belapectin remains highly encouraging with incidence of adverse events and serious adverse events comparable across the three cohorts.

Rates of discontinuation, adverse events (AEs), and serious adverse events (SAEs) were comparable to placebo, with no drug-related SAEs reported in the NAVIGATE trial.

The Company continues to analyze data from the 57 patients that completed 36 months of treatment prior to the ending of the trial in February 2025.

While data from this group would not change the results of the NAVIGATE clinical trial for patients completing 18 months of treatment, the Company believes that any encouraging data from this group of patients may draw interest from potential strategic partners.

In the NAVIGATE trial, as proposed in the protocol, secondary endpoints include a composite clinical outcomes endpoint, including varices requiring treatment (development of large varices or varices with a red wale), decompensating events, all-cause mortality, MELD score increase, liver transplant.

Also, NASH non-invasive biomarkers will be evaluated.

To target a population at risk of developing esophageal varices, patient selection was based on clinical signs of portal hypertension, including, but not limited to, a low platelet count, an increased spleen size, an increased liver stiffness, and/or evidence of abdominal collaterals circulation.

The focus and goal of the therapeutic program is to stop the progression of and/or reverse portal hypertension and thereby prevent the development of varices, potentially one of the most life-threatening complications of cirrhosis.

Based on the results of the NASH-CX trial and subject to confirmation in later stage clinical trials, we believe that this goal is achievable in a significant portion of the NASH cirrhosis patient population i.e.

those NASH cirrhosis patients with clinical signs of portal hypertension for whom, currently, apart from a liver transplantation, no specific liver targeted, treatments are available.

We activated more than 150 clinical trial sites in 14 countries for the NAVIGATE trial.

The COVID-19 pandemic delayed our regulatory and ethics approvals, recruitment of sites, and enrollment of patients for our NAVIGATE trial.

For several reasons, the pandemic made enrolling patients

for the NAVIGATE trial more challenging, notably because patients eligible for the NAVIGATE trial have liver cirrhosis and, as such, were at a greater health risk of complications from COVID-19 and needed to be vaccinated before taking the risk

of infection associated with a visit to a healthcare facility.

As we emerged from the COVID-19 pandemic, site recruitment and patient enrollment accelerated and we experienced increases in the speed of enrollment, particularly in the United

For several reasons, the pandemic made enrolling patients for the NAVIGATE trial more challenging, notably because patients eligible for the NAVIGATE trial have liver cirrhosis and, as such, were at a greater health risk of complications from COVID-19 and needed to be vaccinated before taking the risk of infection associated with a visit to a healthcare facility.

As we emerged from the COVID-19 pandemic, site recruitment and patient enrollment accelerated and we experienced increases in the speed of enrollment, particularly in the United States.

However, we did not see the enrollment in Europe that we anticipated.

Consequently, we activated multiple sites in Latin America.

A resurgence of the COVID pandemic could again delay the regulatory, ethical and clinical milestones that we

need to meet to conduct our NAVIGATE trial.

The last patient from the phase 2b stage was randomized in February 2023, and consequently we expect topline results from the IA late in the fourth quarter of 2024.

Further details on the NAVIGATE trial can be found on www.clinicaltrials.gov under study NCT04365868 and on our NAVIGATE website (navigatenash.com).

The Company also has completed a Hepatic Impairment Study, which ran in parallel with the phase 2b/3 trial as part of the development program.

The Hepatic Impairment Study was conducted

at three sites and involved approximately 40 patients (divided amongst normal healthy volunteers, and patients with hepatic impairment categorized as Child-Turcotte-Pugh (CTP) classes A (mild), B (moderate), and C (severe).

received a single infusion of belapectin (4 mg/kg LBM) and their serum belapectin levels were monitored for up to approximately two weeks to define the effects of various stages of cirrhosis on serum belapectin levels.

The tolerance and safety

of belapectin was evaluated.

Enrollment in this study was completed in February 2022, and the final results were presented at T he Liver Meeting™ 2023, hosted by the American Association for the Study of

Liver Diseases.

The data indicated that belapectin exposure did not increase with the degree of hepatic insufficiency, a property that is consistent with the observed

The information contained therein is not incorporated herein by reference.

Company also has completed a Hepatic Impairment Study, which ran in parallel

with the phase 2b/3 trial as part of the development program.

Impairment Study was conducted at three sites and involved approximately 40

patients (divided amongst normal healthy volunteers, and patients with hepatic

impairment categorized as Child-Turcotte-Pugh (CTP) classes A (mild), B

(moderate), and C (severe).

Each subject received a single infusion of

belapectin (4 mg/kg LBM) and their serum belapectin levels were monitored for

up to approximately two weeks to define the effects of various stages of

cirrhosis on serum belapectin levels.

The tolerance and safety of belapectin

was evaluated.

Enrollment in this study was completed in February 2022, and the

final results were presented the T he Liver Meeting™

2023, hosted by the American Association for the Study of Liver Diseases.

data indicated that belapectin exposure did not increase with the degree of

hepatic insufficiency, a property that is consistent with the observed

distribution of the drug into activated macrophages.

Further details on this hepatic impairment study can be found on www.clinicaltrials.gov study NCT04332432.

Cancer Immunotherapy.

We believe there is potential for galectin inhibition to play a key role in the innovative area of cancer immunotherapy.

For example, there have been several recent approvals of drugs that enhance a patient’s immune system to fight cancer.

It is our goal to use ourgalectin-3 inhibitor to further enhance the immune system function

to help the body to fight cancer in a way that complements other approaches to this type of therapy.

This hypothesis is supported by the fact that galectin-3 is expressed at high levels in multiple types of tumors and their micro-environment,

where it fosters the malignant nature of the tumors, and protects the tumors from immune attack by the patient’s own defense mechanism.

Our drug candidates provide a promising new therapeutic approach to enhance the activity of the immune system

against cancer cells.

Preclinical studies have indicated that belapectin enhances the immune response to cancer cells, increased tumor shrinkage and enhanced survival in immune competent mice with prostate, breast, melanoma and sarcoma cancers

when combined with one of the immune checkpoint inhibitors, anti-CTLA-4 or anti-PD-1, or with the immune cell activator anti-OX40.

These preclinical data led to the filing of two Investigator-sponsored INDs and the initiation of Phase 1B studies

of belapectin in combination with Yervoy ® (ipilimumab) in metastatic melanoma and another phase 1B study in combination with KEYTRUDA (pembrolizumab) in patients

with metastatic melanoma and head and neck squamous cell carcinoma.

These studies were conducted under the sponsorship of Providence Portland Medical Center’s Earle A.

Chiles Research Institute (EACRI).

The phase IB study in combination with Yervoy was rapidly discontinued after the first patients were recruited because of the availability of new treatment in the selected population.

Promising results were reported in the Phase 1b trial combining belapectin with pembrolizumab (KEYTRUDA ® ).

aggregated cohorts are combined, in advanced melanoma, a 50% objective response rate with belapectin in combination with KEYTRUDA, was documented.

In addition, a 33% response rate was documented in patients with head and neck cancer.

have been published in 2021 in a highly rated peer reviewed journal (Curti et al.

details on this hepatic impairment study can be found on www.clinicaltrials.gov

study NCT04332432.

Immunotherapy.

We believe there is potential for galectin

inhibition to play a key role in the innovative area of cancer immunotherapy.

For example, there have been several recent approvals of drugs that enhance

a patient’s immune system to fight cancer.

It is our goal to use ourgalectin-3

inhibitor to further enhance the immune system function to help the body to

fight cancer in a way that complements other approaches to this type of

This hypothesis is supported by the fact that galectin-3 is expressed

at high levels in multiple types of tumors and their micro-environment, where

it fosters the malignant nature of the tumors, and protects the tumors from

immune attack by the patient’s own defense mechanism.

Our drug candidates

provide a promising new therapeutic approach to enhance the activity of the

immune system against cancer cells.

Preclinical studies have indicated that

belapectin enhances the immune response to cancer cells, increased tumor

shrinkage and enhanced survival in immune competent mice with prostate, breast,

melanoma and sarcoma cancers when combined with one of the immune checkpoint

inhibitors, anti-CTLA-4 or anti-PD-1, or with the immune cell activator

These preclinical data led to the filing of two

Investigator-sponsored INDs and the initiation of Phase 1B studies of

belapectin in combination with Yervoy ®

(ipilimumab) in metastatic melanoma and another phase 1B study in combination

with KEYTRUDA (pembrolizumab) in patients with metastatic melanoma and head and

neck squamous cell carcinoma.

These studies were conducted under the

sponsorship of Providence Portland Medical Center’s Earle A.

Chiles Research Institute

phase IB study in combination with Yervoy was rapidly discontinued after the

first patients were recruited because of the availability of new treatment in

the selected population.

results were reported in the Phase 1b trial combining belapectin with

pembrolizumab (KEYTRUDA ® ).

When aggregated

cohorts are combined, in advanced melanoma, a 50% objective response rate with

belapectin in combination with KEYTRUDA, was documented.

In addition, a 33%

response rate was documented in patients with head and neck cancer.

have been published in 2021 in a highly rated peer reviewed journal (Curti et

Journal of Immunotherapy of cancer 2021;9:e002371).

There was also a suggestion that the combination of belapectin with pembrolizumab could decrease the auto-immune

side-effect induced by pembrolizumab.

These side-effects, which are directly linked to the mechanism of action of pembrolizumab, can be poorly tolerated and even severe enough to lead to treatment interruption, even if the effect on the cancer

was encouraging.

This is, a very frustrating situation for patients who have to discontinue an active treatment but have no other options available to them.

We believe these data, taken together with the observed favorable safety and tolerability

of the combination, provide a rationale to move the belapectin program in oncology forward.

Late in 2021, we engaged three noted physicians – Dr.

Chetan Bettegowda, from Johns Hopkins, and Dr.

There was also a

suggestion that the combination of belapectin with pembrolizumab could decrease

the auto-immune side-effect induced by pembrolizumab.

These side-effects, which

are directly linked to the mechanism of action of pembrolizumab, can be poorly

tolerated and even severe enough to lead to treatment interruption, even if the

effect on the cancer was encouraging.

This is, a very frustrating situation for

patients who have to discontinue an active treatment but have no other options

available to them.

We believe these data, taken together with the observed

favorable safety and tolerability of the combination, provide a rationale to

move the belapectin program in oncology forward.

in 2021, we engaged three noted physicians – Dr.

Chetan Bettegowda, from Johns

Hopkins, and Dr.

Nishant Agrawal and Dr.

Ari Rosenberg, both from University of Chicago Medical Center – as

consultants to help define the path forward in oncology.

In consultation with our oncology experts, we have now selected the treatment of recurrent or metastatic head and neck cancer as the lead indication to pursue for belapectin in combination

with an immune checkpoint inhibitor.

The decision is notably based on the lack of available treatments for these patients, the limited number of therapies in development, and the resulting very high medical need.

We filed an IND with FDA and are

planning a phase 2 trial to be filed with the FDA oncology division.

Ari Rosenberg, both from University of

Chicago Medical Center – as consultants to help define the path forward in

In consultation with our oncology experts, we have now selected the

treatment of recurrent or metastatic head and neck cancer as the lead

indication to pursue for belapectin in combination with an immune checkpoint

The decision is notably based on the lack of available treatments

for these patients, the limited number of therapies in development, and the

resulting very high medical need.

We filed an IND with FDA and are planning a

phase 2 trial to be filed with the FDA oncology division.

Results of Operations

Three and Nine Months Ended September 30, 2024 Compared to Three and Nine Months Ended September 30, 2023

Three Months Ended March 31, 2025 Compared to Three Months Ended March 31, 2024

Research and Development Expense.

Three Months Ended

Nine Months Ended

Ended March 31,

2025 as Compared to 2024

September 30,

(In thousands, except %)

Research and development

We generally categorize research and development expenses as either direct external expenses, comprised of amounts paid to third party vendors for services, or all other research and development

expenses, comprised of employee payroll and general overhead allocable to research and development.

We consider a clinical program to have begun upon acceptance by the FDA, or similar agency outside of the United States, to commence a clinical

trial in humans, at which time we begin tracking expenditures by the product candidate.

Clinical program expenses comprise payments to vendors related to preparation for, and conduct of, all phases of the clinical trial, including costs for drug

manufacture, patient dosing and monitoring, data collection and management, oversight of the trials and reports of results.

Pre-clinical expenses comprise all research and development amounts incurred before human trials begin, including payments

to vendors for services related to product experiments and discovery, toxicology, pharmacology, metabolism, and efficacy studies, as well as manufacturing process development for a drug candidate.

We generally categorize research and development expenses as either direct external expenses, comprised of amounts paid to third party vendors for services, or all other research and development expenses, comprised of employee payroll and general overhead allocable to research and development.

We consider a clinical program to have begun upon acceptance by the FDA, or similar agency outside of the United States, to commence a clinical trial in humans, at which time we begin tracking expenditures by the product candidate.

Clinical program expenses comprise payments to vendors related to preparation for, and conduct of, all phases of the clinical trial, including costs for drug manufacture, patient dosing and monitoring, data collection and management, oversight of the trials and reports of results.

Pre-clinical expenses comprise all research and development amounts incurred before human trials begin, including payments to vendors for services related to product experiments and discovery, toxicology, pharmacology, metabolism, and efficacy studies, as well as manufacturing process development for a drug candidate.

Our research and development expenses were as follows:

Three Months Ended

Nine Months Ended

September 30,

Direct external expenses:

(in thousands)

Clinical programs

Direct external expenses:

Clinical activities

Pre-clinical activities

All other research and development expenses

Clinical activities increased primarily due to timing of incurrence of expenditures related to our NAVIGATE clinical trial.

Pre-clinical activities decreased primarily due to the timing of certain

projects and activities in support of clinical programs.

Other research and development expenses increased primarily due to additional employees hired after the first and second quarters of 2023.

Both the time required and costs we may incur in order to commercialize a drug candidate that would result in material net cash inflow are subject to numerous variables, and therefore we are unable at

this stage of our development to forecast useful estimates.

Variables that make estimates difficult include the number of clinical trials we may undertake, the number of patients needed to participate in the clinical trial, patient recruitment

uncertainties, trial results as to the safety and efficacy of our product, and uncertainties as to the regulatory agency response to our trial data prior to receipt of marketing approval.

Moreover, the FDA or other regulatory agencies may suspend

clinical trials if we or an agency believes patients in the trial are subject to unacceptable risks or find deficiencies in the conduct of the clinical trial.

Delays or rejections may also occur if governmental regulation or policy changes during

our clinical trials or in the course of review of our clinical data.

Due to these uncertainties, accurate and meaningful estimates of the ultimate cost to bring a product to market, the timing of costs and completion of our program and the period

during which material net cash inflows will commence are unavailable at this time.

Clinical activities decreased primarily due to timing of incurrence of expenditures related to our NAVIGATE clinical trial which ended in the first quarter of 2025.

Variables that make estimates difficult include the number of clinical trials we may undertake, the number of patients needed to participate in the clinical trial, patient recruitment uncertainties, trial results as to the safety and efficacy of our product, and uncertainties as to the regulatory agency response to our trial data prior to receipt of marketing approval.

Moreover, the FDA or other regulatory agencies may suspend clinical trials if we or an agency believes patients in the trial are subject to unacceptable risks or find deficiencies in the conduct of the clinical trial.

Delays or rejections may also occur if governmental regulation or policy changes during our clinical trials or in the course of review of our clinical data.

Due to these uncertainties, accurate and meaningful estimates of the ultimate cost to bring a product to market, the timing of costs and completion of our program and the period during which material net cash inflows will commence are unavailable at this time.

General and Administrative Expense.

Three Months Ended

Nine Months Ended

Ended March 31,

2025 as Compared to 2024

September 30,

(In thousands, except %)

General and administrative

General and administrative expenses consist primarily of salaries including stock-based compensation, legal and accounting fees, insurance, investor relations, business development and other office

related expenses.

The primary reason for the increase in general and administrative expenses for the three-months ended September 30, 2024 as compared to the same period in 2023 is due to a decrease in investor relations/business development.

The primary reasons for the decrease in general and administrative expenses for the nine-months ended September 30, 2024 as compared to the same period in 2023 is due to a decrease in legal expense and investor relations/business development

General and administrative expenses consist primarily of salaries including stock-based compensation, legal and accounting fees, insurance, investor relations, business development and other office related expenses.

The primary reasons for the decrease in general and administrative expenses for the three-months ended March 31, 2025 as compared to the same period in 2024 is due to decreases in investor relations/business development of $65,000 and decrease in non-cash stock based compensation expenses of approximately $91,000.

Liquidity and Capital Resources

Since our inception on July 10, 2000, we have financed our operations from proceeds of public and private offerings of debt and

As of September 30, 2024, we raised a net total of $314.5 million from these offerings.

At September 30, 2024, the Company had $27.1 million of unrestricted cash and cash equivalents.

In addition, on November 14, 2024, the Company

entered into a second supplemental unsecured $6 million line of credit financing with its chairman, Richard E.

Uihlein (see note 9).

The Company believes there is sufficient cash to fund currently planned operations approximately through May,

These factors raise substantial doubt about the Company’s ability to continue as a going concern for a period of 12 months from the issuance date of this Form 10-Q.

The ability of the Company to continue as a going concern is likely

dependent on the top line results of the Company’s NAVIGATE clinical trial expected in December 2024 and its ability to raise capital;

however, the Company’s cash position may not be sufficient to support its daily operations after May 2025.

will require more cash to fund our operations after May, 2025 and believe we will be able to obtain additional financing.

The currently planned operations include costs related to our NAVIGATE clinical trial .

However, there can be no assurance that we will be successful in obtaining such new financing or, if available, that such financing will be on terms favorable to us.

Net cash used in operations increased by $713,000 to $28,976,000 for the nine months ended September 30, 2024, as compared to $28,263,000 for the nine months ended September 30,

Cash operating expenses increased principally due to timing of payment of expenses related to our NAVIGATE clinical trial with belapectin.

Since our inception on July 10, 2000, we have financed our operations from proceeds of public and private offerings of debt and equity.

As of March 31, 2025, we raised a net total of $314.5 million from these offerings.

At March 31, 2025, the Company had $7.4 million of unrestricted cash and cash equivalents in addition to $11 million remaining available under two lines of credit provided by our chairman available to fund future operations.

The Company believes there is sufficient cash to fund currently planned operations through August 2025.

We will require more cash to fund our operations after August 2025.

There can be no assurance that we will be successful in obtaining such new financing or, if available, that such financing will be on terms favorable to us.

Net cash used in operations decreased by $4,415,000 to $7,689,000 for the three months ended March 31, 2025, as compared to $12,105,000 for the three months ended March 31, 2024.

Cash operating expenses increased principally due to the preparations and expenses related to our NAVIGATE clinical trial with belapectin.

Off-Balance Sheet Arrangements

We have not created, and are not a party to, any special-purpose or off-balance sheet entities for the purpose of raising capital, incurring debt or operating parts of our business that are not

consolidated into our financial statements.

We do not have any arrangements or relationships with entities that are not consolidated into our financial statements that are reasonably likely to materially affect our liquidity or the availability

of capital resources.

We have not created, and are not a party to, any special-purpose or off-balance sheet entities for the purpose of raising capital, incurring debt or operating parts of our business that are not consolidated into our financial statements.

Application of Critical Accounting Policies and Estimates

The preparation of condensed consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, expenses, and related disclosure of

contingent assets and liabilities.

The preparation of condensed consolidated financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, expenses, and related disclosure of contingent assets and liabilities.

On an ongoing basis, we evaluate our estimates, including those related to accrued expenses, stock-based compensation, contingencies and litigation.

We base our estimates on historical experience, terms of

existing contracts, our observance of trends in the industry, information available from other outside sources and on various other factors that we believe to be appropriate under the circumstances.

Actual results may differ from these estimates

under different assumptions or conditions.

We base our estimates on historical experience, terms of existing contracts, our observance of trends in the industry, information available from other outside sources and on various other factors that we believe to be appropriate under the circumstances.

Actual results may differ from these estimates under different assumptions or conditions.

Critical accounting policies are those policies that affect our more significant judgments and estimates used in preparation of our consolidated financial statements.

We believe our critical

accounting policies include our policies regarding stock-based compensation, accrued expenses and income taxes.

We believe our critical accounting policies include our policies regarding stock-based compensation, accrued expenses and income taxes.

For a more detailed discussion of our critical accounting policies, please refer to our 2024 Annual Report on Form 10-K.

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-Q

Item 2. Management’s Discussion and Analysis