Business Overview and History
Tharimmune, Inc. is a clinical-stage biotechnology company committed to developing innovative therapeutic candidates that address high unmet needs in the fields of immunology and inflammation. With a diverse pipeline spanning rare, inflammatory, and oncologic conditions, Tharimmune is strategically positioned to make a significant impact on patient outcomes.
Tharimmune was incorporated on March 28, 2017 as a Delaware-based C-corporation, formerly operating under the name Hillstream BioPharma, Inc. The company was founded with the mission to develop therapeutic candidates for rare, inflammatory, and oncologic conditions with high unmet need. In September 2023, the company underwent a name change to Tharimmune, reflecting its evolving focus on immunology and inflammation.
In November 2023, Tharimmune entered into a landmark patent license agreement with Avior Inc. dba Avior Bio, LLC, securing exclusive global rights to develop and commercialize two of its lead product candidates, TH104 and TH103. This agreement granted Tharimmune an exclusive sublicensable right and license to develop, manufacture, and commercialize these products. TH104, the company's most advanced program, is a transmucosal buccal film formulation designed to treat moderate-to-severe chronic pruritus, or severe itching, associated with primary biliary cholangitis (PBC), a rare and debilitating liver disease.
Tharimmune's pipeline also includes TH023, an oral anti-tumor necrosis factor-alpha (TNF-α) monoclonal antibody, licensed from Intract Pharma in September 2024. This strategic partnership aims to leverage Intract's proprietary drug delivery platforms to develop an oral formulation of the widely used biologic therapy infliximab.
In addition to its clinical-stage assets, Tharimmune is advancing an early-stage pipeline of novel therapeutic candidates targeting high-value immuno-oncology (IO) targets, including human epidermal growth factor receptor 2 (HER2), human epidermal growth factor receptor 3 (HER3), and programmed cell death protein 1 (PD-1). The company's expertise in developing antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and small molecular weight bovine-derived Picobodies has positioned it to address challenging, "undruggable" epitopes.
Tharimmune's strategic partnerships and license agreements have been pivotal in strengthening its pipeline and technological capabilities. In July 2023, the company entered into a research collaboration and license agreement with Applied Biomedical Science Institute (ABSI), gaining exclusive rights to develop and commercialize ABSI's products targeting the ErbB2 (HER2) and ErbB3 (HER3) receptors. This collaboration has enabled Tharimmune to advance its HER2/HER3-targeted bispecific antibody, TH3215, towards IND-enabling studies.
The company's commitment to innovation is further underscored by its acquisition of a global license from Enkefalos Biosciences in June 2024 to develop products related to cyclotides, a novel class of compounds with the potential to deliver HER2 antibodies across the blood-brain barrier. This strategic move has expanded Tharimmune's pipeline and reinforced its position as a leader in the development of transformative therapies.
Tharimmune faced several challenges early in its history as a private company. In 2019, the company acquired a series of small molecule analogues which required an initial payment of $50,000 upon raising at least $2 million in funding, with up to $1.75 million in potential milestone payments. Additionally, Tharimmune entered into research collaboration and license agreements with Minotaur Therapeutics, Inc. and Taurus Biosciences, LLC in 2023 to advance its Picobody platform against PD-1.
In January 2022, Tharimmune completed its initial public offering, raising approximately $12.5 million in gross proceeds. This provided important funding to advance the company's pipeline of therapeutic candidates. However, Tharimmune has continued to face liquidity challenges, concluding that the prevailing conditions and ongoing liquidity risks raise substantial doubt about its ability to continue as a going concern.
Financial Overview
Tharimmune has primarily financed its operations through public and private equity offerings, including its initial public offering (IPO) in January 2022, which generated net proceeds of approximately $12.5 million. The company has also completed several follow-on offerings, including a $2.1 million public offering in May 2023 and an $8.7 million public offering in November 2023. In June 2024, Tharimmune raised an additional $1.8 million through a private placement.
For the fiscal year 2023, Tharimmune reported a net loss of $9.32 million. As of September 30, 2024, Tharimmune reported cash and cash equivalents of $4.77 million, compared to $10.94 million as of December 31, 2023. The company's net loss for the nine months ended September 30, 2024, was $8.38 million, compared to a net loss of $6.85 million for the same period in 2023. For the most recent quarter (Q3 2024), Tharimmune reported a net loss of $3.8 million, primarily driven by increased research and development expenses related to the advancement of clinical programs and higher general and administrative costs.
Tharimmune's research and development expenses for the nine months ended September 30, 2024, were $4.31 million, compared to $2.57 million for the same period in 2023. The increase was primarily driven by the advancement of the company's clinical programs, including the completion of the Phase 1 trial for TH104 and increased licensing fees.
General and administrative expenses for the nine months ended September 30, 2024, were $4.28 million, compared to $4.36 million for the same period in 2023. The slight decrease was primarily due to lower investor relations and insurance costs, partially offset by an increase in personnel costs and director remuneration.
Tharimmune's operating cash flow for the nine months ended September 30, 2024, was negative $7.87 million, compared to negative $5.88 million for the same period in 2023. The increased cash burn was primarily attributable to the company's continued investment in research and development activities and the expansion of its pipeline.
Liquidity and Capital Resources
As of September 30, 2024, Tharimmune had $4.77 million in cash and cash equivalents, compared to $10.94 million as of December 31, 2023. The company's working capital as of September 30, 2024, was $3.02 million, compared to $9.13 million as of December 31, 2023.
Tharimmune's current ratio and quick ratio as of September 30, 2024, were both 2.35, indicating that the company has sufficient short-term assets to cover its short-term liabilities. However, the company's limited operating history, recurring negative cash flows from operations, and current plans have led management to conclude that there is substantial doubt about Tharimmune's ability to continue as a going concern for at least one year following the date of its latest financial statements.
As of September 30, 2024, Tharimmune had an accumulated deficit of $33.1 million. The company may seek to raise additional funding through the sale of equity or debt securities, strategic partnerships, or other arrangements to support its future operations.
Product Pipeline and Development Strategy
Tharimmune's key product segments and pipeline include:
TH104 and TH103: Through the patent license agreement with Avior in November 2023, Tharimmune gained exclusive rights to develop and commercialize these candidates globally. TH104 has a dual mechanism of action targeting multiple receptors known to suppress chronic, debilitating pruritus. The company plans to first seek approval for TH104 in the treatment of moderate-to-severe chronic pruritus in patients with primary biliary cholangitis (PBC). Tharimmune expects to obtain topline data from a Phase 2 trial with TH104 in PBC in Q4 2025. For TH103, the company intends to develop the product candidate and potentially file an investigational new drug (IND) application.
Oral Anti-TNF-α Program: In September 2024, Tharimmune licensed the global development and commercialization rights (outside of South Korea) for INT-023/TH023, an oral anti-TNF-α monoclonal antibody, from Intract Pharma. This agreement also grants Tharimmune access to Intract's Soteria and Phloral delivery platforms and an existing supply agreement for infliximab to be used in the oral product development program.
Immuno-Oncology Pipeline: Tharimmune is developing an early-stage pipeline targeting validated high-value immuno-oncology targets, including HER2, HER3, and PD-1. The company is advancing TH3215, a bispecific antibody targeting both HER2 and HER3, into IND-enabling studies in 2025. Additionally, TH0059, a HER2-HER3 bispecific antibody-drug conjugate (bsADC), and TH1940, a PD-1 Picobody, are expected to progress to IND-enabling studies in 2025.
Regulatory Updates and Clinical Milestones
In February 2023, Tharimmune received FDA approval for an investigational new drug (IND) application for its lead candidate, TH104. The company is currently preparing to initiate a Phase 2 clinical trial evaluating TH104 for the treatment of moderate-to-severe chronic pruritus in patients with primary biliary cholangitis (PBC), a rare and chronic liver disease.
In October 2024, Tharimmune announced that it had received positive feedback from a Scientific Advice meeting with the European Medicines Agency (EMA) regarding the planned Phase 2 and Phase 3 clinical development of TH104. The Agency noted that the company's proposed regulatory pathway, using a hybrid application approach, is acceptable and could enable referring to non-clinical and some safety data from approved products.
Tharimmune has also presented positive data from the Phase 1 clinical trial of TH104 at several medical conferences, including the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting and the American Association for the Study of Liver Disease (AASLD) The Liver Meeting® 2024. The data demonstrated that TH104 was well-tolerated with a favorable safety profile, supporting the company's plans to advance the program into a Phase 2 trial.
Market Opportunity and Industry Trends
The pruritus treatment market is expected to grow at a compound annual growth rate (CAGR) of approximately 8% over the next five years. This growth is driven by the increasing need for effective therapies to manage chronic itch associated with various underlying conditions, including primary biliary cholangitis.
Tharimmune's focus on developing innovative treatments for chronic pruritus and other inflammatory conditions positions the company to capitalize on this growing market opportunity. The company's lead candidate, TH104, addresses a significant unmet need in the treatment of moderate-to-severe chronic pruritus associated with PBC, a rare liver disease with limited treatment options.
Risks and Challenges
Tharimmune, like many clinical-stage biotechnology companies, faces a range of risks and challenges that could impact its future performance and success:
1. Clinical development risks: The company's ability to successfully complete clinical trials and obtain regulatory approvals for its product candidates is critical to its long-term success. Delays or failures in the clinical development process could significantly impact Tharimmune's timeline and financial resources.
2. Funding and liquidity concerns: Tharimmune's current cash position and recurring negative cash flows from operations raise substantial doubt about its ability to continue as a going concern. The company's ability to secure additional funding through equity or debt offerings, strategic partnerships, or other arrangements will be crucial to its continued operations and pipeline advancement.
3. Competitive landscape: Tharimmune operates in highly competitive therapeutic areas, with other biotechnology and pharmaceutical companies developing similar or competing treatments. The company's success will depend on its ability to differentiate its products and maintain a competitive edge.
4. Intellectual property protection: The company's ability to protect its proprietary technologies and product candidates through patents, trade secrets, and other measures is essential to maintaining its competitive position. Any challenges to Tharimmune's intellectual property rights could adversely affect its business.
5. Reliance on third-party partners and suppliers: Tharimmune's dependence on third-party contractors, such as contract research organizations (CROs) and contract manufacturing organizations (CMOs), to conduct its clinical trials and manufacture its product candidates exposes the company to operational and supply chain risks.
6. Regulatory and compliance requirements: As a biopharmaceutical company, Tharimmune must navigate complex and evolving regulations, which could lead to delays, increased costs, or failure to obtain necessary approvals for its product candidates.
Tharimmune's management team is actively working to address these risks and challenges through strategic partnerships, robust clinical development programs, and prudent financial management. The company's ability to execute on its plans and overcome these obstacles will be crucial to its long-term success and the delivery of innovative therapies to patients in need.
Conclusion
Tharimmune is a clinical-stage biotechnology company at the forefront of developing transformative therapies in the fields of immunology and inflammation. With a diverse pipeline, a focus on addressing high unmet medical needs, and a commitment to innovation, the company is well-positioned to make a significant impact on patient outcomes.
The company's lead candidate, TH104, is progressing through clinical development for the treatment of moderate-to-severe chronic pruritus associated with primary biliary cholangitis, a rare and debilitating liver disease. Tharimmune's strategic partnerships and license agreements have further strengthened its pipeline and technological capabilities, enabling the advancement of additional clinical-stage and early-stage programs.
While Tharimmune faces the inherent risks and challenges common to clinical-stage biotechnology companies, including funding concerns and clinical development uncertainties, its experienced management team, robust R&D expertise, and dedication to innovation provide a foundation for potential long-term success. As the company continues to execute on its strategic priorities and navigate the regulatory landscape, it remains focused on delivering on its mission of pioneering therapies that address unmet needs and improve the lives of patients.