18 Jun The Emerging Paradigm in HIV Therapeutics Offers Hope for a Cure
Human Immunodeficiency Virus (HIV) compromises the body’s immunity by attacking CD4 cells (a type of T cell), exposing it to a host of infections and diseases and ultimately leading to the development of AIDS. According to data provided by Centres for Disease Control and Prevention, an estimated 1.1 million people in the U.S are afflicted with this disease and 1 in 7 or 15% of those affected are unaware of their condition. In 2017, over 38,739 people were diagnosed with HIV and 6 dependant areas and nearly 15,807 deaths were registered among people diagnosed with HIV.
Advances in treatment and care, such as development of antiretroviral therapy (ART), have increased the life expectancy of people diagnosed with HIV and helped arrest the disease from progressing to AIDS, with an estimated 20.9 million people on ART as of 2017. There is no cure for the disease as yet, with existing therapeutic options seeking to stop the progression of the disease and alleviating symptoms.
Antiretroviral therapy can be categorised as highly active antiretroviral therapy (HAART) or combination antiretroviral therapy (cART), however they can cause adverse reactions, severe toxicity and exacerbate existing co-morbidities. Scientific advancements have led to the discovery and development of protease inhibitors, integrase inhibitors, nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), chemokine co-receptor antagonists and entry inhibitors that seek to overcome the limitations of the existing treatment options.
According to a report by GlobalData, the global HIV market will reach $22.5 billion by 2025 growing at a CAGR of 3% from $16.3 billion in 2015.
We take a look at some companies which are striving to find a solution for this menace by using cutting-edge technology with improved safety, tolerability and toxicity profiles.
CytoDyn (OTCMKTS: CYDY)
Market Cap: $143.32M; Current Share Price: 0.4351 USD
Data by YCharts
Its lead candidate for the treatment of HIV is Leronlimab (PRO 140), a fully humanized IgG4 monoclonal antibody directed against CCR5, otherwise known as viral-entry inhibitors. This acts by blocking the HIV (R5) subtype entry into T-cells, used by HIV as a molecular portal, and masking the CCR5 co-receptor, but leaving its ability to provide an immune response intact. Though it does not exhibit agonist activity towards CCR5, it has demonstrated antagonist activity to CCL5, a central mediator in inflammatory diseases.
So far the company has conducted over 7 clinical trials for Leronlimab (PRO 140) that have proven its ability to reduce HIV viral load in patients, offering minimal side-effects and lower dosages as compared to conventional medicine.
In April 2019, CytoDyn announced the topline results from its Phase 2b monotherapy trial. In addition, it filed an application for an investigational new drug application (IND) with a Phase 3 protocol for a monotherapy trial with the FDA. The study will be conducted by Amarex Clinical Research, its principal CRO. It is currently engaged in a crucial Phase 3 trial for Leronlimab (PRO 140), as an adjunct therapy to HAART (Highly Active Anti-Retroviral Therapy). Additionally, it has also initiated a Phase 2 trial for treatment of Graft versus Host Disease (GvHD), in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who are undergoing bone marrow stem cell transplantation. CytoDyn also plans to file for an Orphan Drug Designation for Colon Cancer.
It is pursuing 8 cancer indications and NASH and intends to launch preclinical studies in Melanoma, Pancreatic Cancer, Breast, Prostate, Colon, Lung, Liver and Stomach Cancer.
Matinas BioPharma, (NYSE: MTNB)
Market Cap: $114.39M; Current Share Price: 0.80 USD
Data by YCharts
Matinas Biopharma’s proprietary lipid nano-crystal (LNC) intracellular drug delivery platform facilitates the delivery of a broad range of small molecules, nucleic acid polymers, proteins, peptides, vaccines, and targeted delivery of gene editing technologies. The platform can deliver drug candidates intracellularly, through activated target cells such as immune cells or virally infected cells, both orally and through IV. It can reformulate IV administered drugs as oral agents to offer a better safety profile, enhance their efficacy and reduce toxicity.
It is developing MAT2203, an orally administered LNC formulation of amphotericin B (a broad spectrum fungicidal agent) for the treatment of cryptococcal meningitis in HIV/AID, which was granted Fast Track and Qualified Infectious Disease Product (QIDP) designations by the FDA. The candidate is being developed under non-dilutive funding from the NIH through key efficacy milestones.
Matinas Biopharma is planning to launch a Phase 2 study in patients with cryptococcal meningitis in the second half of 2019. The company recently announced that it has entered into research collaboration with ViiV Healthcare, to evaluate the LNC platform delivery technology for formulations of select antivirals that have the potential to cure HIV, but are held back due to issues concerning intracellular delivery and high levels of toxicity.
The company owns a GMP manufacturing facility that offers scalability with 90% encapsulation efficiency.
Its pipeline consists of MAT2203, which is currently under phase I development for the prevention of IFI in Acute Lymphoblastic Leukemia, MAT2501 for the treatment of Non-Tuberculous Mycobacterium (NTM) Infections and MAT9001 for Hypertriglyceridemia.
Zion Medical (Private)
Zion, an Israeli biotechnology company dedicated to bringing path-breaking solutions to the unmet needs in AIDS and Cancer research, is developing “Gammora”, an Investigational Medicinal Product. It is a synthetic peptide compound, derived from the HIV enzyme integrase, which is responsible for encasing the DNA with the Virus’s genetic material in an infected cell. The peptide is produced by PolyPeptide Labs and has the potential to cure those suffering from this menace, by destroying all cells carrying the HIV virus-genome.
The results from its first clinical trial show that it can eliminate up to 99% of the HIV Virus within four weeks of treatment, by promoting apoptosis. The compound can promote the integration of multiple HIV DNA fragments into the host cell’s genomic DNA, leading to the self-destruction of the infected cell. The drug has shown to be well tolerated and safe, with no side-effects. The company is upbeat about the results and intends to replicate its success in a Phase 2b trial with a larger number of participants.
Its proprietary technology is based on the work of Dr. Abraham Loyter, a professor at the Hebrew University of Jerusalem, who holds the patents for the peptide (U.S. Patent No. 9163067, 9738878). The company in-licensed the compound and has been engaged in its development through pre-clinical and clinical stages. It has filed an additional patent with the U.S. Patent and Trademark Office in August 2018, for an updated version of the peptide and final drug composition.
Gilead Sciences, (NASDAQ:GILD)
Market Cap: $84.46B; Current Share Price: 66.42 USD
Data by YCharts
The company which already markets anti-HIV-1 medication namely Atripla®, (efavirenz 600 mg/emtricitabine 200 mg/ tenofovir disoproxil fumarate 300 mg), BIKTARVY (bictegravir, emtricitabine, and tenofovir alafenamide.), COMPLERA((emtricitabine, rilpivirine, tenofovir disoproxil fumarate) to name a few is developing multiple candidates for the treatment of HIV/AIDS such as Emtricitabine and tenofovir alafenamide for the treatment of PrEP, GS-9131, a nucleoside analog reverse transcriptase inhibitor (NRTI) ; GS-6207, a capsid inhibitor ; Vesatolimod, a TLR-7 agonist and GS-9722, a bNab for the treatment of HIV/AIDS.
It recently celebrated 10 years of providing innovative generic licensing agreements for its HIV drugs to multiple manufacturers, which has helped drive down generic treatment costs, by almost 80% since 2006. The company is the first Innovator to become a part of the Medicines Patent Pool, with its drugs being registered in over 114 developing countries, and over 18 generic manufacturers being given the license to produce Gilead’s HIV Drugs, in countries such as India, South Africa and China.
The company offers a 360 degree approach to encompass the awareness, science, research and treatment of HIV in developing countries. Its single tablets regimens are designed to lower the cost of HIV therapy even further. Scientists at Gilead are working at finding a cure for the disease by not only developing pre-exposure prophylaxis (PrEP) as a prevention tool, but also exposing dormant HIV-infected cells to the body’s immune system, so that it can mount an attack.
It has built a robust network of partnerships with NGO’s, government organisations and public health organizations to impart HIV training to nurses, doctors and public health workers and is one of the top corporate funder of HIV/AIDS programs globally.
Gilead also offers a chimeric antigen receptor T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma named Yescarta, a kinase inhibitor called Zydelig, an oral formulation of an endothelin receptor antagonist indicated for use in pulmonary arterial hypertension named Letairis and an antifungal agent called AmBisome to name a few. The company has an extensive pipeline consisting of numerous candidates under development for treatment of disorders such as Lupus, Liver diseases, Hematology and Oncology, Cardiovascular and Inflammatory or Respiratory disorders.
It has a strong network of strategic collaborations with companies such as Bristol-Myers Squibb Company (NYSE: BMY), Janssen Sciences Ireland UC, Japan Tobacco (TYO: 2914), Galapagos NV (NASDAQ: GLPG), Scholar Rock Holding Corporation (NASDAQ: SRRK), Tango Therapeutics, Pfizer (NYSE:PEE), Sangamo Therapeutics (NASDAQ: SGMO), Gadeta B.V, HiFiBiO Therapeutics, Agenus (NASDAQ: AGEN), and Insitro Inc.
Enochian Biosciences (NASDAQ: ENOB)
Market Cap: $213.15M; Current Share Price: 5.49 USD
Data by YCharts
This Clinical stage biopharmaceutical company is developing novel therapeutics using its gene-modified cell therapy platform for the treatment of HIV/AIDS and Cancer. It primarily focuses on preventative vaccine and cures for HIV and cellular immune-oncology products for prevention of relapse of metastatic colon cancer. The company’s novel approach allows for the engraftment of the gene-modified human stem cells that can prohibit the expression of CCR5 and eliminate CD4 + T cells. In addition, to seeking to eliminate the need for ART it is also studying the possibility of using immunotherapy as a preventive vaccination. Enochian is also working on improving the stimulatory capacity of Dendritic Cells by genetic modification.
It pipeline consists of ENOB-HV-01, that is currently under preclinical development stage for the treatment of HIV, ENOB-HV-11, a preventive HIV Vaccine and ENOB-HV-12 meant as a therapeutic HIV Vaccine. It is also pursuing ENOB-DB as a possible treatment for Pancreatic, triple negative breast cancer, glioblastoma and renal cell carcinoma.
The company has entered into strategic collaborations with Scripps Research, to conduct synergeneic and humanized mice studies and advance preclinical work in preparation, for filing an IND with the FDA for its HIV programs. UCLA and Enochain have signed an R&D agreement to evaluate gene-modification techniques to make human population resistant to HIV. In addition, it has an agreement with Hitachi Chemical Advanced Therapeutics Solutions (HCATS) for a manufacturing assessment of ENO-1001.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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