mernabg.png

OUR PROGRAMS

Merlin's Priority.jpg

Oncology

 

MERLIN Biotech's oncology program focuses on novel intra-tumoral immunotherapy agents that drive both a local immune response against tumors while enhancing systemic immune activation. Intra-tumoral injection allows highly localized treatment while potentially decreasing the systemic toxicity seen with traditional administration routes.

MERLIN Biotech's lead oncology therapeutic, an mRNA encoding the protein USP6, has been licensed from the Children’s Hospital of Philadelphia and has demonstrated efficacy in multiple murine models. Unlike traditional immunotherapies that only affect one or two targets, USP6 simultaneously triggers numerous immune-stimulatory pathways within the cancer cell. This multi-pronged attack leads to enhanced recruitment and activation of multiple immune lineages including T cells, NK cells, and macrophages, thereby potentially increasing the likelihood of a durable patient response.

MERLIN Biotech's USP6 technology potentially offers a broad potential market across multiple indications including liver (700K), breast (330K), ovarian (22K), lymphoma (86K), melanoma (80K), head/neck (65K), sarcomas (12K) with a potential combined market size of more than $100 billion by mid-2020. In addition, USP6 has shown strong activity in a rare pediatric cancer known as Ewing sarcoma (500 patients/year), which is eligible for both the orphan drug designation and the rare pediatric disease priority review voucher (valued at approximately $100 million).

In addition, MERLIN Biotech is also developing a novel 2nd generation STING agonist, licensed from the Baruch S. Blumberg Institute, as well as novel intra-tumoral macrophage and natural killer cell modulators.

Chronic Hepatitis B

 

Currently more than 260 million people worldwide are chronically infected with hepatitis B despite an effective vaccine since the 1980’s. For these people, the preventive vaccine has no therapeutic value. 

People living with CHB are unable to “clear” the virus because of an inadequate or “exhausted” immune response to viral antigens. Current medicines can suppress viral replication and reduce the number of infected cells in a person’s liver; however, even after ten years of daily therapy, infected cells continue to cause inflammation that can result in progressive liver disease leading to death. Notably, cessation of therapy almost always results in viral recurrence. 

Without a curative therapy, up to 20% of people with living with chronic hepatitis B (CHB) will die prematurely from liver cirrhosis or liver cancer. Although currently approved drugs for chronic hepatitis B can reduce the risk of morbidity and mortality, they require lifelong use and are not curative.

The current annual global market of hepatitis B drugs is expected to reach $5.16bn by 2029 at a compound annual growth rate (CAGR) of 3.1% in the nine major markets (US, Germany, France, Italy, Spain, the UK Japan, Brazil and China) (https://www.globaldata.com/chronic-hepatitis-b-market-set-reach-5-16bn-2029-says-globaldata/.

Confidence in this market has recently been demonstrated in Gilead’s more than $1.4 billion acquisition of Myrcludex B, a drug recently approved in Europe for treating hepatitis Delta virus, representing a subset of about 10-20% of chronic hepatitis B infections.

MERLIN Biotech’s mRNA-based therapeutics for chronic hepatitis B aims to break immune tolerance. MERLIN’s modified mRNA-specifying sub-dominant viral epitopes delivered to antigen presenting cells via IM injection and/or mRNA specifying functions (neoantigens) selectively expressed in liver cells of people with chronic hepatitis B (CHB) may help break immune tolerance and allow viral clearance. 

Preventive Vaccines 

 

Lyme Disease

Lyme disease is the most common tick-borne disease in North America, Europe, and Asia. In the United States alone, there are an estimated 476,000 cases of Lyme disease diagnosed and treated each year, according to the U.S. Centers for Disease Control and Prevention (CDC). There is currently no approved vaccine and no effective treatment. 

MERLIN Biotech seeks to develop a mRNA-based preventive vaccine against Lyme disease by using the established mechanism of action of inducing serum antibodies to the outer surface protein A (OspA). This is produced by the infecting tick that allows passage of the pathogenic Borrelia sp. bacteria to gain access to the human body. It has been demonstrated that a specific serum antibody titer or concentration to OspA will induce protection from Lyme disease. 

Expression of the tick outer surface protein A (OspA) by encoded mRNAs in the antigen presenting cells should reliably induce a protective level of antibody. Previously marketed Lyme disease vaccines used this mechanism, and the exact titer of antibody has been established. There are also two animal models that would allow rapid preclinical testing and proof of concept.  Importantly, MERLIN is using a proprietary vaccine formulation that is expected to produce higher and more durable antibody titers than previous strategies. This increased immunogenicity of the Merlin Lyme vaccine should make it best in class and the preferred product.

Climate change is thought to be responsible for the geographic expansion of high- incidence zones for Lyme disease with a recent study showing a 45% increase since 1998. The socioeconomic costs of Lyme disease in the U.S. are currently estimated at more than $2 billion per year. An effective and publicly accepted vaccine would likely dramatically reduce the costs associated with Lyme disease. 

Tick Borne Encephalitis

Tick-borne encephalitis (TBE) is a human viral infectious disease involving the central nervous system and widely occurs in Europe and Asia. The vast majority of infections with the virus result from infected ticks, found in woodland habitats, which often remain firmly attached to the skin for days. On rare occasions, infection can result from consumption of unpasteurized milk from infected goats, sheep or cows. 

There is no direct person-to-person transmission. Approximately 10 000–12 000 clinical cases TBE are reported each year, but this figure is believed to be significantly lower than the actual total number of clinical cases.

There is no specific drug therapy for TBE. Meningitis, encephalitis, or meningoencephalitis requires hospitalization and supportive care based on syndrome severity. Anti-inflammatory drugs, such as corticosteroids, may be considered under specific circumstances for symptomatic relief.

MERLIN strategy for an effective and durable Lyme vaccine would also apply to a similar vaccine against TBE.