Tharimmune Announces Phase 2 Study Plan for TH104 in Patients With Moderate-to-Severe Pruritus Associated With Primary Biliary Cholangitis and Provides a Business Update

 

Source:  Tharimmune, Inc. 12/16/2024

Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company committed to pioneering therapies in immunology and inflammation, today announced plans for initiating a Phase 2 study evaluating TH104 in patients suffering from moderate-to-severe pruritus (severe itching) associated with primary biliary cholangitis (PBC), a rare and chronic liver disease, and also provided a corporate update. The launch of this clinical trial, expected in 2025, follows favorable results from Tharimmune's Phase 1 study with TH104, recent regulatory feedback from the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), as well as progress on manufacturing clinical study supply.

Business Update and 2024 Corporate Highlights

Throughout 2024 Tharimmune achieved significant milestones across three key areas. These accomplishments reflect progress in advancing innovative therapies in inflammation and immunology, with a focus on improving patient outcomes in areas of high unmet need.

Manufacturing, Clinical and Regulatory Progress

• Validation and batches of manufacturing supply of TH104 for Phase 2 clinical study are on track for year-end.

• Announced positive results from a Phase 1 clinical trial of TH104 in healthy subjects, demonstrating a favorable pharmacokinetic profile and a mild side-effect profile.

• Received positive regulatory feedback from the FDA and EMA for the TH104 clinical program, providing guidance on the Phase 2 trial design.

• Granted a patent from the European Patent Office covering therapeutics created for carrying antibody and peptide therapies, representing a novel solution and addressing critical challenges with stability and absorption.

Medical and Scientific Community Engagement

• Participated in key industry conferences to present new clinical data and engage with the scientific community.

• Presented favorable clinical data at the American College of Gastroenterology (ACG) Annual Scientific Meeting, reinforcing the safety profile of TH104 with no unexpected treatment-emergent adverse events.

• Shared positive clinical data at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting^®, highlighting a significant correlation between blood levels and symptom relief in patients treated with TH104.

Corporate Achievements

• Entered into a licensing agreement with Intract Pharma, aiming to expand Tharimmune's product pipeline to develop oral biologics including an oral formulation of infliximab.

• Entered into a licensing agreement with OmniAb, accessing their antibody discovery technology platform to enhance Tharimmune's early-stage immunology pipeline.

• Appointed David Jones, Professor of Liver Immunology at Newcastle University in England and renowned scientist with extensive expertise in hepatic pathologies and PBC, to Tharimmune's Scientific Advisory Board.

• Completed private placement financings, raising more than $4 million to support clinical development and working capital, including TH104 development program.

TH104 Phase 2 Clinical Study

The multicenter, randomized, double-blind, placebo-controlled Phase 2 trial is designed to assess the safety, tolerability and efficacy of TH104 in reducing itch in PBC patients with moderate-to-severe pruritus, a condition that significantly impacts daily lives and remains an area of unmet medical need. The study plans to enroll approximately 40 patients at sites in the U.S., Europe and the UK. Patients will receive escalating doses of TH104 in a nine-week study that includes treatment and observation periods, with efficacy measured by changes in patient-reported itch scores utilizing the Worst-Itch Numerical Rating Scale (WI-NRS), a relevant clinical outcome assessment for pruritus, as well as other quality-of-life metrics. Additional information on the Phase 2 study is available on ClinicalTrials.gov (NCT06733519).

"Following feedback from global regulators including guidance on a future Phase 3 program, we are delighted to advance TH104 into this Phase 2 clinical trial planned for 2025, marking a critical milestone in our efforts to address the debilitating effects of chronic pruritus. Our focus on innovative delivery mechanisms that target the opioid receptors involved in the body's itch circuitry underscores the favorable data collected thus far in clinical development. We plan to report preliminary results from this Phase 2 trial in late 2025," said Randy Milby, Chairman and CEO of Tharimmune.

Board of Directors Expansion

Additionally, Tharimmune announced the appointment of Sanam Parikh to its Board of Directors, expanding the size of its Board to six Directors. Mr. Parikh brings to Tharimmune significant experience in clinical trial management, regulatory submissions and operational oversight.

Mr. Parikh has managed clinical studies across various global sites, overseeing CRO partnerships and site management to ensure compliance with complex regulatory standards. His experience includes site feasibility, budget negotiation, contract management and regulatory interactions, with particular expertise working under FDA and EMA guidelines. Earlier in his career, Mr. Parikh was an associate clinical project manager in oncology at Clario, and held various research laboratory positions prior to that.

"Sanam is an emerging leader in preclinical and clinical study management. His background in oncology-focused clinical operations along with a proven record in managing critical aspects of trial execution will significantly bolster our capabilities," added Mr. Milby. "Furthermore, his in-depth knowledge of clinical operations and his focus on ensuring study integrity from preclinical work through to regulatory submissions aligns with our strategic goals as we continue to develop and validate our oncology-focused product pipeline."

Mr. Parikh holds a Master's in Public Health with a focus on Urban Public Health from Rutgers University, and a Bachelor's in Biology from the New Jersey Institute of Technology.

About TH104

TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.

About Pruritus and Primary Biliary Cholangitis

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a rare and chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. Pruritus is a common condition associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a debilitating impact on health-related quality of life with limited treatment options.Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates in immunology, inflammation and oncology. Its lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers.

Tharimmune Presents Positive Clinical Data at AASLD the Liver Meeting(R) to Support TH104 for Chronic Pruritus in Chronic Liver Disease

 

Source:  Tharimmune, Inc. 11/18/2024

Significant correlation shown between blood levels and symptom relief; TH104 was well tolerated with no unexpected treatment-emergent adverse events

Phase 2 preliminary data for chronic pruritus in primary biliary cholangitis expected in 2025

Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation and immunology, presented new TH104 clinical data at the American Association for the Study of Liver Disease (AASLD) The Liver Meeting^® 2024, underway in San Diego from November 15-19. The Phase 1 trial was a single-dose, single-center, open-label, randomized study of TH104 transmucosal buccal film conducted in two cohorts of patients with chronic liver disease (CLD), with the primary outcome of safety and tolerability.

"This presentation at The Liver Meeting expands the audience for encouraging Phase 1 data with our lead candidate TH104," said Randy Milby, CEO of Tharimmune. "We look forward to initiating a Phase 2 multiple-ascending dose trial in the coming months to evaluate TH104 in chronic pruritus in primary biliary cholangitis (PBC) patients, with topline data expected in 2025. In the meantime, we continue to engage with both U.S. and EU regulatory authorities."

Data presented at The Liver Meeting include adverse events (AEs) as well as an assessment of patients' relief of pruritus symptom scores when correlated to pharmacokinetics (PK) of TH104. Patients with cholestatic liver disease and a known history of persistent generalized pruritus for at least 4 weeks prior to screening were included. After an overnight fast of 10 hours, subjects received a single low dose of TH104. Serial blood samples for PK analysis were taken, and patients were monitored for itch severity scores utilizing the Worst-Itch Numerical Rating Scale (WI-NRS), a relevant clinical outcome assessment for pruritus in chronic liver disease, and for itch intensity over a 24-hour period.

Pruritus is common in most liver diseases and the WI-NRS is a validated numerical rating scale displaying 11 numbers ranging from 0, representing "no itch," to 10, representing "worst imaginable itch," and patients are asked to pick the number corresponding to the intensity of their pruritus. Results from multiple large studies support the usefulness and validity of WI-NRS for evaluating change over time in clinical trials. Pearson's correlation coefficient (r) was used to assess the correlation between TH104 concentration (ng/ml) Area Under the Curve (AUC) and the change in WI-NRS score 48 hours after dosing.

This study screened 19 patients and 12 were enrolled with two types of CLD categorized as Child-Pugh A (cohort A) and Child-Pugh B (cohort B). The Child-Pugh score is a system for assessing the prognosis and necessity of transplant in CLD that provides a forecast of the increasing severity of a patient's liver disease and expected survival rate. The score is determined by scoring clinical measures of liver disease and the possibility of eventual liver failure, with Class A indicating mild liver disease and Class B indicating moderate liver disease with one-to-five-year survival rates of 95% and 75%, respectively. There were no patients enrolled in this study with the most severe Child-Pugh C classification.

The correlation coefficient between TH104 AUC and change in itch, r, was 0.7060, with a p-value of 0.0103 and a 95% confidence interval for r of 0.2220 to 0.9108.

Change in Itch Score vs. Pharmacokinetics of TH104

The mean baseline WI-NRS scores in Groups A and B were 4.33 and 6.17, respectively, translating to moderate-to-severe chronic pruritus at the start of the study. The mean baseline itch score for all 12 subjects was 5.25. At one-hour post-dosing with TH104, Group A and Group B had a mean decline in WI-NRS scores of 26.8% and 19.0%, respectively, and continued to decline two hours post-dose by 42.3% and 21.7%, respectively. Both cohorts continued to improve in mean itch scores at the four-hour and eight-hour time points, including the combined total subjects. At 24-hours post dosing, Group A and Group B achieved a mean decline of 30.7% and 35.2%, respectively, in pruritus scores. The mean reduction in itch scores for all 12 subjects 24 hours after a single dose of TH104 was 33.3%.

WI-NRS score over time

A total of two AEs (headache) were reported in two subjects over the course of the study. These AEs were mild and possibly related to study drug, with no serious adverse events reported. There were no deaths or other significant adverse events reported during the entire study. There were no new adverse events during the study, with events correlated with previous studies and a safety profile consistent with the literature for the active ingredient in TH104.

About TH104

TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.

About Pruritus and Primary Biliary Cholangitis

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. The disease, believed to be an autoimmune condition, affects an estimated 58 out of every 100,000 U.S. women and about 15 out of every 100,000 U.S. men. Pruritus is one of the most common conditions associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a negative impact on health-related quality of life with limited treatment options.Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates in immunology, inflammation and oncology. Its lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers.

Tharimmune Granted European Patent for Delivery of Optimized Molecularly Targeted Therapeutics

 

Source:  Tharimmune, Inc. 11/13/2024

Tharimmune, Inc. (NASDAQ:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation and immunology, announced today that the European Patent Office intends to grant the Company a patent covering biodegradable polymeric nanoparticles created for carrying therapeutic and targeting agents. With particular utility in cancer therapies, this innovative platform is designed to enhance the delivery of therapeutic antibodies and peptides, which are often limited by enzymatic degradation and poor systemic circulation.

The patent covers the design, preparation and therapeutic application of nanoparticles formed from biodegradable block copolymers. These nanoparticles exhibit tunable size, non-toxic profiles and the ability to prolong drug half-life in the bloodstream. By penetrating biological barriers and delivering encapsulated drug directly to disease sites, reduces systemic side effects and toxicity while improving the therapy's effectiveness. An application for a comparable U.S. patent has been submitted to the United States Patent and Trademark Office, and is currently under review.

"Molecularly targeted therapies are effective alternatives to conventional treatments, but challenges remain in delivering these antibody-based and peptide drugs. We believe our system represents a novel solution, addressing critical challenges with stability and absorption," said Randy Milby, Chief Executive Officer of Tharimmune. "We believe the platform can become an important component of future therapies, and receipt of this European patent marks an exciting first step."

This new patent complements Tharimmune's existing pipeline, including colonic targeting developed through the Company's partnership with Intract Pharma. While Tharimmune initially focused on tablet-based solutions for lower gastrointestinal delivery, this new intellectual property represents a potential platform to complement its growing pipeline. Tharimmune is also actively exploring strategic partnerships with companies that specialize in antibody conjugation to further enhance the targeting capabilities of its platform.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates in immunology and inflammation. The lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers.

Tharimmune Announces $2.02 Million Private Placement to Advance Development Programs

 

Source:  Tharimmune, Inc.  12/6/2024

Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company committed to pioneering therapies in immunology and inflammation, today announced it has entered into a securities purchase agreement to raise gross proceeds of approximately $2.02 million through a private placement.

The agreement includes the issuance of 961,446 shares of common stock (or common stock equivalents) and warrants to purchase up to an additional 480,723 shares of common stock. Each share (or common stock equivalent) is priced at $2.10 and is accompanied by a warrant. The warrants will have an exercise price of $2.031 per share, becoming exercisable six months after issuance and expiring five and one-half years from the date of issuance. The closing of this transaction is expected on or about December 9, 2024, subject to customary closing conditions.

Strategic Investors and Placement Details

The financing was led by Gravitas Capital and SDS Capital Group, alongside other biotechnology-focused private investors. President Street Global served as the exclusive placement agent for the offering, ensuring seamless execution of the transaction.

After deducting placement agent fees and other offering-related expenses, the Company intends to allocate the net proceeds toward clinical development, including advancing its flagship TH104 development program, as well as general working capital.

Advancing Innovation in Biotechnology

This financing reinforces Tharimmune's commitment to advancing its portfolio of therapeutic candidates. TH104, the Company's lead clinical asset, is designed to address chronic pruritus associated with primary biliary cholangitis (PBC), a rare and challenging autoimmune liver disease.

Regulatory Details

The securities in this private placement were offered under Section 4(a)(2) of the Securities Act of 1933, as amended, and Regulation D thereunder. The shares of common stock and underlying warrants are not registered under the Securities Act or state securities laws. The Company has agreed to file a resale registration statement covering these securities to enable their future trading upon registration or qualification under applicable laws.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company focused on developing innovative therapies in immunology, inflammation, and oncology. The Company's lead product candidate, TH104, leverages a unique transdermal buccal film technology designed to address inflammatory conditions, including pruritus associated with PBC. Tharimmune is also advancing TH023, an oral TNF-alpha inhibitor, and exploring novel multi-specific biologics targeting solid tumors. Through a licensing agreement with OmniAb, Inc., the Company harnesses cutting-edge antibody discovery platforms to target specified disease markers.

Tharimmune Presents Favorable TH104 Phase 1 Clinical Data at the American College of Gastroenterology 2024 Annual Scientific Meeting

 Source:  Tharimmune, Inc. 10/28/2024

TH104, the Company's lead candidate for moderate-to-severe pruritus in chronic liver disease, showed no opioid withdrawal effects, reinforcing safety profile

TH104 was well tolerated with no unexpected treatment-emergent adverse events, supporting further clinical development

Company expects Phase 2 topline data for chronic pruritus in primary biliary cholangitis (PBC) patients in 2025

Tharimmune, Inc. (Nasdaq:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation and immunology, presented new TH104 Phase 1 data at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting, underway in Philadelphia. The Phase 1 trial was a single-dose, single-center, open-label, randomized study of TH104 transmucosal buccal film conducted in two cohorts of patients with chronic liver disease (CLD). The primary outcome measure was to determine the safety and tolerability of a single buccal dose of TH104 in these patients.

COWS Score

The data presented included adverse events (AEs) as well as assessment of patients using the Clinical Opiate Withdrawal Scale (COWS). The COWS is an 11-item clinician-administered scale that can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor them over time. The summed score for the complete scale can be used by clinicians to determine the stage or severity of withdrawal, and to assess the level of any physical dependence.

This study enrolled two types of CLD patients categorized as Child-Pugh A (cohort A) and Child-Pugh B (cohort B). The Child-Pugh score is a system for assessing the prognosis and necessity of transplant in CLD that provides a forecast of the increasing severity of a patient's liver disease and expected survival rate. The score is determined by scoring clinical measures of liver disease and the possibility of eventual liver failure, with Class A indicating mild liver disease and Class B indicating moderate liver disease with a one-to-five-year survival rates of 95% and 75%, respectively. There were no patients enrolled in this study with the most severe Child-Pugh C classification.

The mean baseline WI-NRS scores in Groups A and B were 4.33 and 6.17, respectively, translating to moderate-to-severe chronic pruritus at the start of the study. The mean baseline itch score for all 12 subjects was 5.25. At one hour post-dosing with TH104, Group A and Group B had a mean decline in WI-NRS scores of 26.8% and 19.0%, respectively, and continued to decline two hours post-dose by 42.3% and 21.7%, respectively. Both cohorts continued to improve in mean itch scores at the four-hour and eight-hour time points, including the combined total subjects. At 24-hours post dosing, Group A and Group B achieved a mean decline of 30.7% and 35.2%, respectively, in pruritus scores. The mean reduction in itch scores for all 12 subjects 24 hours after a single dose of TH104 was 33.3%.

There were no deaths, other serious adverse events or other significant adverse events reported during the entire study. There were no new adverse events during the entire study, with events correlated with previous studies and a safety profile consistent with the literature for the active ingredient in TH104.

"We are pleased with the totality of the Phase 1 data with TH104, which build upon previous studies demonstrating reliable and predictable delivery of nalmefene using our proprietary microparticle embedded transmucosal delivery system. This system is easily applied to the inside of the cheek within seconds in healthy volunteers. The mean 33.3% reduction in itch scores just 24 hours after a single dose of TH104 demonstrates the potential for rapid symptomatic relief," said Randy Milby, CEO of Tharimmune. "The data presented today in liver disease further strengthen our confidence in the potential of TH104 to address pruritis, a debilitating symptom for these patients."

The Company plans to initiate a Phase 2 multiple-ascending dose trial in the coming months to assess the safety and tolerability of TH104, which will assess the change from baseline in WI-NRS scores to evaluate chronic pruritus in PBC patients. The Company expects topline data in 2025 and is engaging with both U.S. and EU regulatory authorities.

About TH104

TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that easily adheres to the inside of the mouth. This endows TH104 with key features making it an ideal product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.

About Pruritus and Primary Biliary Cholangitis

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. The disease, believed to be an autoimmune condition, affects an estimated 58 out of every 100,000 U.S. women and about 15 out of every 100,000 U.S. men. Pruritus is one of the most common conditions associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a negative impact on health-related quality of life with limited treatment options. Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates in immunology and inflammation. The lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers.

Tharimmune Receives Positive Regulatory Feedback From EMA for TH104 Clinical Program for Chronic Pruritus in Primary Biliary Cholangitis

 

Source:  Tharimmune, Inc. 10/30/20204

Tharimmune, Inc. (NASDAQ:THAR) ("Tharimmune" or the "Company"), a clinical-stage biotechnology company developing a portfolio of therapeutic candidates in inflammation and immunology, received positive feedback from a Scientific Advice meeting with the European Medicines Agency (EMA) that included guidance on a planned Phase 2 trial to advance TH104, the Company's lead clinical-stage candidate for moderate-to-severe pruritus in primary biliary cholangitis (PBC).

The EMA interactions specifically focused on both the Phase 2 and Phase 3 clinical program of TH104. Overall, the Agency noted that using Article 10(3), hybrid application, is acceptable and could enable referring to non-clinical and some safety data from the approved products. Regarding non-clinical information provided, the Agency endorsed the strategy presented by the Company and noted that there is no need to conduct additional animal studies and considered human exposure to be adequate to move forward. The Agency found the design and main features of the proposed Phase 2 study overall acceptable with some comments. The Agency also provided general guidance for the design of a future Phase 3 study.

"We are pleased with our interactions with both the FDA and EMA," said Randy Milby, CEO of Tharimmune. "The recent regulatory feedback from the EMA builds on the previous positive interactions with the FDA while providing a roadmap for TH104 for chronic pruritus in PBC, which continues to be a debilitating symptom for patients suffering from this rare condition. The progress with regulatory agencies is a testament to our continued commitment to advance innovative solutions in inflammation and immunology."

The Company plans to initiate a Phase 2 multiple-ascending dose trial in the coming months to assess the safety and tolerability of TH104, which will also assess the change from baseline in itch scores to evaluate chronic pruritus in PBC patients. The Company expects topline data in 2025 and continues to engage with both U.S. and EU regulatory authorities.

About TH104

TH104 is embedded with nalmefene onto a proprietary transdermal buccal film that adheres to the inside of the mouth. TH104 is a product candidate for multiple liver-related and other pruritogenic inflammatory conditions. The molecule has a dual mechanism of action affecting both the µ-opioid receptor and the kappa-opioid receptor, as well as potentially inhibiting IL-17 inflammatory cytokine expression. These opioid receptors when stimulated and/or inhibited by the body's natural ligands have been known to be involved in the body's itch circuitry.

About Pruritus and Primary Biliary Cholangitis

According to the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health, PBC is a chronic disease where the bile ducts in the liver eventually become dysfunctional and cause the buildup of bile, resulting in liver damage. The disease, believed to be an autoimmune condition, affects an estimated 58 out of every 100,000 U.S. women and about 15 out of every 100,000 U.S. men. Pruritus is one of the most common conditions associated with PBC, affecting up to 75% of individuals at some point during their disease course. It has a negative impact on health-related quality of life with limited treatment options. Published survey data of PBC respondents suffering from pruritus described their itch as "bugs crawling under the skin." More than 65% of patients reported that the itch was worse at night, known as nocturnal pruritus, a high unmet need.

About Tharimmune

Tharimmune, Inc. is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates in immunology and inflammation. The lead clinical asset, TH104, aims to suppress chronic pruritus associated with primary biliary cholangitis (PBC), a rare autoimmune liver disease with no known cure. The expanded pipeline includes TH023, an oral TNF-alpha inhibitor, offering a new approach to treating autoimmune diseases. Tharimmune is also advancing early-stage multi-specific biologics targeting unique epitopes against multiple solid tumors. The company has a license agreement with OmniAb, Inc. to access their antibody discovery technology for targeting specified disease markers.

Comstock Sells Northern Mining Targets to Mackay Precious Metals Inc.

 

Source:  Comstock, Inc. 12/20/2024

Comstock Inc. (NYSE: LODE) (“Comstock” and the “Company”) today announced it has executed a Membership Interest Purchase Agreement (the “MIPA”) to sell 100% of the northernmost patented and unpatented mining claims, mineral exploration rights and town lots (the “Northern Targets”) currently owned by Comstock’s wholly-owned subsidiary Comstock Northern Exploration, LLC., plus all of the 25% issued and outstanding membership interest that Comstock owns in Pelen LLC (“Pelen”) to Mackay Precious Metals Inc. (“Mackay”) for an aggregate purchase price of $2.75 million (the “Purchase Price”) and a 1.5% NSR production royalty from the sales of silver, gold, and all other valuable minerals and products extracted from these properties, in perpetuity.

The Company was paid $1.3 million in cash with another $0.45 million due before February 15, 2025, plus an additional $1.0 million that will be paid within 45 days of the completion of Mackay’s public listing, at the election of Mackay, in either cash or their publicly registered common shares. The monetized value of $1.0 million from the public listed shares is guaranteed by the value date of October 31, 2025.

On June 30, 2023, Comstock executed a Mineral Exploration and Mining Lease Agreement (“Mackay Lease”) with Mackay. Since June 30, 2023, Comstock has received cash of $3.2 million in initial and ongoing lease payments and will also receive an additional, final pro-rata lease payment associated with these properties of $0.5 million before February 15, 2025. The $3.7 million in total lease payments are in addition to the $2.75 million sale price. The parties terminated the Mackay Lease on December 18, 2024.

The Northern Targets encompass both the Gold Hill and Occidental Lode claim groups in Storey County, Nevada. Pelen owns certain claims adjacent to and/or relevant to these northern claim groups.

“Our Northern Targets were never an effective part of our district-wide development plans, so realizing nearly $6.5 million in consideration from this lease and subsequent sale, plus the retention of royalties in perpetuity, is extremely positive for Comstock, especially as we activate our plans for advancing the S-K 1300 compliant Dayton Consolidated and permitted Lucerne resources, and more aggressively expand the gold and silver potential in the southern part of the district,” said Corrado De Gasperis, Comstock’s executive chairman and chief executive officer. “We are bullish on our gold and silver resources, especially as both our hard rock and metal recycling activities aggressively expand into this silver cycle.”

About Comstock Inc.

Comstock Inc. (NYSE: LODE) commercializes innovative technologies that contribute to global decarbonization and the clean energy transition by efficiently converting under-utilized natural resources, primarily, woody biomass into low-carbon renewable fuels, end-of-life metal extraction and renewal, and generative AI-enabled advanced materials synthesis and mineral discovery for sustainable mining. To learn more, please visit www.comstock.inc.