Tharimmune, Inc. (NASDAQ:THAR) is a clinical-stage biotechnology company developing a diverse portfolio of therapeutic candidates targeting high-value indications in inflammation and immunology. The company's lead asset, TH104, is poised to address the significant unmet need for effective treatments of chronic pruritus, or uncontrollable itching, in patients with primary biliary cholangitis (PBC), a rare and debilitating liver disease. With a robust pipeline of novel multi-specific antibodies and a strategic focus on underserved conditions, Tharimmune is well-positioned to deliver innovative solutions and drive value for shareholders.

Business Overview

Tharimmune was incorporated in March 2017 and has since established itself as a promising player in the biotechnology landscape. The company's core focus is on developing therapeutic candidates that address high-unmet-need conditions in the areas of inflammation and immunology. Tharimmune's lead clinical-stage asset, TH104, is a transmucosal buccal film formulation of nalmefene, a mu-opioid and kappa-opioid receptor modulator, designed to suppress chronic, debilitating pruritus in PBC patients.

In addition to TH104, Tharimmune is advancing an early-stage pipeline of novel multi-specific antibodies targeting validated 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). These innovative therapies leverage Tharimmune's license agreement with OmniAb, Inc. to access their proprietary antibody discovery technology platform.

Financials

For the fiscal year ended December 31, 2023, Tharimmune reported an annual net loss of $9,319,094 and no revenue, reflecting the company's focus on research and development activities. The company's annual operating cash flow and free cash flow were both negative $7,300,106, as it continues to invest in the advancement of its pipeline.

In the first quarter of 2024, Tharimmune reported a net loss of $2,256,109, with no revenue generated during the period. Research and development expenses for the quarter were $1,025,258, while general and administrative expenses were $1,322,045. The company's cash position as of March 31, 2024, stood at $8,427,290, providing a runway to support its ongoing operations and development efforts.

Pipeline and Clinical Progress

Tharimmune's lead candidate, TH104, is a novel transmucosal buccal film formulation of nalmefene, a mu-opioid and kappa-opioid receptor modulator. The company recently completed a positive Phase 1 clinical trial with TH104, which demonstrated a comparable safety and tolerability profile to the FDA-approved intravenous formulation of nalmefene. Tharimmune is now in discussions with the FDA regarding the design of a Phase 2 clinical trial for TH104 in the treatment of moderate-to-severe chronic pruritus in PBC patients, which it expects to initiate in the third quarter of 2024.

PBC is a rare and chronic liver disease characterized by the progressive destruction of bile ducts, leading to the accumulation of bile and other toxins in the liver. Chronic pruritus, or uncontrollable itching, is a debilitating symptom experienced by more than 70% of PBC patients, for which there are currently no approved treatments. Tharimmune believes TH104's unique mechanism of action, targeting both mu-opioid and kappa-opioid receptors, has the potential to effectively suppress this distressing symptom and improve the quality of life for PBC patients.

In addition to TH104, Tharimmune is advancing a pipeline of novel multi-specific antibodies targeting high-value IO targets. The company's lead IO candidate, TH3215, is a bispecific antibody that binds to both HER2 and HER3 receptors, targeting a novel "bridging epitope" encompassing multiple domains of the HER2 extracellular domain. Tharimmune anticipates that TH3215 will progress to IND-enabling studies in 2025, followed by the potential advancement of TH0059, a HER2/HER3 bispecific antibody-drug conjugate, and TH1940, a PD-1 Picobody, into IND-enabling studies in the same year.

Competitive Landscape and Differentiation

The chronic pruritus associated with PBC represents a significant unmet medical need, as there are currently no approved treatments for this debilitating symptom. Tharimmune's TH104 has the potential to be the first therapy specifically developed and approved for the treatment of chronic pruritus in PBC patients. The company's unique transmucosal buccal film formulation of nalmefene is designed to provide a convenient and effective treatment option, potentially improving patient adherence and quality of life.

In the IO space, Tharimmune's multi-specific antibody candidates, including TH3215, TH0059, and TH1940, aim to address the limitations of traditional monoclonal antibodies by targeting multiple epitopes and receptors simultaneously. This approach has the potential to enhance efficacy and overcome resistance mechanisms in various solid tumor types.

Liquidity

Tharimmune has historically financed its operations through public and private offerings of its equity securities. In 2023, the company completed two successful public offerings, raising net proceeds of approximately $2.1 million in the May Offering and $8.7 million in the November Offering. As of March 31, 2024, Tharimmune had $8.4 million in cash, which the company believes will be sufficient to fund its operations and development activities through the end of 2024.

However, the company has concluded that the prevailing conditions and ongoing liquidity risks it faces raise substantial doubt about its ability to continue as a going concern for at least one year following the date of its latest financial statements. Tharimmune may need to seek additional funding through the sale of equity or debt securities, strategic partnerships, or other arrangements to support its future operations and the advancement of its pipeline.

Risks and Challenges

Tharimmune, like any clinical-stage biotechnology company, faces a variety of risks and challenges that could impact its future success. These include the inherent uncertainties of drug development, the potential for delays or failures in clinical trials, regulatory approval hurdles, competition from other therapies, and the need to secure additional funding to support its operations and pipeline development.

Specifically, the company's lead candidate, TH104, is still in the early stages of clinical development, and there is no guarantee that it will successfully navigate the regulatory approval process or demonstrate the desired efficacy and safety profile in larger clinical trials. Additionally, Tharimmune's early-stage IO pipeline candidates will require significant investment and time to advance through IND-enabling studies and clinical trials, adding to the company's capital requirements and development timeline.

Outlook

Despite the challenges, Tharimmune remains well-positioned to capitalize on the significant opportunities in the inflammation and immunology therapeutic landscape. The company's lead candidate, TH104, has the potential to address the unmet need for effective treatments of chronic pruritus in PBC patients, a condition that significantly impacts the quality of life for those affected. Additionally, Tharimmune's innovative multi-specific antibody pipeline targeting high-value IO targets holds promise for addressing treatment resistance and improving outcomes in various solid tumor types.

Conclusion

As Tharimmune continues to advance its pipeline and navigate the regulatory landscape, the company's ability to secure additional funding will be crucial to sustaining its operations and driving the development of its promising therapeutic candidates. Investors will closely monitor the company's progress, particularly the upcoming Phase 2 trial for TH104 and the advancement of its IO pipeline, as Tharimmune strives to deliver innovative solutions and create value for shareholders.