Product Pipeline

Product
Preclinical
Phase I
Phase II
Phase III
ALT-801
NASH
HepTcell™
Chronic Hepatitis B
ALT-702
Immunostimulant
NasoVax™
Seasonal Influenza
NasoShield™
Anthrax
 

Programs

Liver Diseases

ALT-801

ALT-801 is a novel peptide-based dual GLP-1/glucagon receptor agonist designed to treat the underlying metabolic dysfunction that leads to non-alcoholic steatohepatitis (NASH). NASH is the most severe form of non-alcoholic fatty liver disease (NAFLD) characterized by abnormal accumulation of fat in the liver, toxic lipid metabolites, inflammation and liver cell damage leading to fibrosis. ALT-801 acts earlier in liver disease progression than other NASH candidates in development and has the potential to reverse metabolic and liver dysfunction as demonstrated in relevant animal models.

Mechanism of Action

ALT-801 activates both the GLP-1 receptor and the glucagon receptor which suppresses appetite and increases energy expenditure resulting in weight loss. ALT-801 has a similar mechanism of action as the body's natural dual acting hormone, oxyntomodulin shown to lower food intake, stimulate energy expenditure and reduce body weight. It is designed to achieve glycemic control comparable to or better than the approved GLP-1 agonists but with more robust weight loss outcomes and once-weekly dosing.

Preclinical Data

ALT-801 demonstrated superior outcome measures in comparison to semaglutide (an approved GLP-1 agonist) and elafibranor (a PPAR alpha/delta agonist) in the biopsy-proven, AMLN-diet Gubra NASH mouse model. In NASH diet-induced obese mouse models, twelve weeks of treatment with ALT-801 (10nmol/kg SC, QD) demonstrated a 25% weight loss in obese mice compared to only 10% with semaglutide (10nmol/kg SC, QD), despite similar food intake. Elafibranor (78μmole/kg, PO) also produced weight decrease under these conditions, but historically this effect has not translated to weight decrease in clinical trials. ALT-801 significantly decreased whole-body fat mass with minimal effect on lean tissue. Histology revealed a near complete absence of liver steatosis, lobular inflammation and ballooning, as well as a superior impact on fibrosis.

Altimmune plans to advance ALT-801 into Phase 1 development.

HepTcell™

HepTcell is an immunotherapeutic product candidate for patients chronically infected with the hepatitis B virus (“HBV”). It is designed to drive CD4+ and CD8+ T-cell responses against all HBV genotypes in patients of all ethnic backgrounds. Stimulating T cell responses in chronically infected HBV patients has been challenging because chronic infection with HBV strongly diminishes T cell immunity directed against the virus.

Mechanism of Action

HepTcell focuses the immune system on discrete, highly conserved regions of the HBV proteome. We believe our approach allows HepTcell to break immune tolerance by activating T cells against critical viral sequences with decreased probability of immune escape due to viral mutation. HepTcell is based on fully synthetic peptide technology and is given by intramuscular injection.

Clinical Data

In 2018 we completed a Phase 1 trial in the United Kingdom and South Korea in patients with chronic HBV. The HepTcell Phase 1 trial was a double-blinded, placebo-controlled, randomized, dose-escalation trial that enrolled 60 subjects with chronic HBV who were HBeAg-negative and well-controlled on licensed antivirals. A total of 40 patients received one of two dose levels of HepTcell, with and without IC31™, a depot-forming TLR9 targeting adjuvant developed by Valneva SE, while 20 control patients received either placebo or IC31 alone. All patients received three injections each 28 days apart and were followed for six months after the final dose. All dose combinations showed excellent tolerability and met the primary endpoint of safety. In the two adjuvanted HepTcell arms, T cell responses against HBV markedly increased over baseline compared to placebo. Altimmune plans to advance HepTcell into Phase 2 development.

HepTcell: Anti-HBV T-cell Response After 3 Injections

Cancer Immunotherapy

ALT-702

ALT-702 is a targeted tumor immunostimulant product candidate that comprises of a highly potent and selective dual TLR7/8 agonist conjugate designed to overcome the safety limitations of other tumor immune stimulants. ALT-702 is being developed to act locally to reverse local immunosuppression within the tumor microenvironment and stimulate antitumor immune responses. ALT-702 also has the potential to synergize with other local and systemic treatment modalities. Altimmune is currently progressing with the preclinical development plan.

Mechanism of Action

Small molecule immunostimulants, including the TLR7/8 dual agonist in ALT-702, can potently stimulate the immune system into action against tumors or pathogens. The potential of these molecules has been limited by the systemic immune stimulations that occurs as the small molecule stimulant diffuses from the site of administration and causes generalized systemic inflammation leading to a loss in safety.  Our approach is to couple the TLR7/8 immunostimulant to proprietary peptides that under the conditions found in a tumor cause the peptides to for a large complex to anchor the immunostimulant to the site of administration for a specific and localized immune stimulation.

Repeat use of immunostimulators in therapeutic settings:

Repeat use of immunostimulators in therapeutic settings

Influenza Vaccine

NasoVAX™

NasoVAX is an intranasal vaccine for both seasonal and pandemic influenza. NasoVAX, an intranasally administered recombinant influenza vaccine, expresses the influenza antigen inside cells following vaccination, thereby stimulating an immune response that is both longer lasting and broader than traditional influenza vaccines. Traditional injected influenza vaccines are unable to elicit mucosal or cellular immune responses, depending solely on the IgG antibody response to block and control influenza virus infection. The data from our Phase 2a trial indicated that NasoVAX was well-tolerated at all doses tested. Additionally, the achievement of 100% seroprotection and statistically significant increases in mucosal antibody at two of the three dose levels studied has set NasoVAX apart from other intranasally administered vaccines. Strong T-cell responses were also observed at the highest dose. This combination of serum antibody, mucosal antibody and T-cell responses provides the potential for improved ability to prevent infection and suggests that NasoVAX could have a greater impact on flu symptoms and shedding of the flu virus than currently approved influenza vaccines. All subjects were followed for six months after vaccination to assess the durability of the antibody response and several subjects from the highest dose were also evaluated between 12 and 14 months after initial dosing for additional immunogenicity assessment. These new NasoVAX data, obtained from the group of 8 subjects that returned for analysis show that the immune response elicited by NasoVAX remained at seroprotective levels for at least 13 months. Durable responses on the order of 1 year are not expected from currently approved influenza vaccines and suggest that immune response induced by NasoVAX could be protective much longer than the current influenza vaccines.

Market Size

According to the CDC, approximately 146 million doses of seasonal influenza vaccine were administered in the US during the 2016-2017 influenza season. The average cost of one dose of a classical inactivated influenza vaccine ranges from approximately $15-18 in the private sector, representing a total addressable market of approximately $2 billion. However, the CDC reports that only 40% of Americans received influenza vaccination in recent years, while recommending a goal of 70% vaccination coverage. The expected increase in US and worldwide vaccinations are expected to result in a worldwide flu vaccine market of $10.2 billion by 2022.

NasoShield™

Altimmune is developing NasoShield as a first-in-class recombinant anthrax vaccine designed to provide rapid, stable protection after a single intranasal administration. It is being developed with the support of the U.S. Biomedical Advanced Research and Development Authority, (“BARDA”) for pre-exposure prophylaxis against anthrax following exposure to aerosolized B. anthracis spores.

After an individual has been exposed to infectious anthrax spores, vegetative B. anthracis bacteria proliferate and release toxins within the host. Although antibiotic therapy is required to eliminate vegetative bacteria, vaccination is necessary to protect against the germination of dormant spores that can occur after termination of antibiotic therapy. This product is a virally vectored rPA vaccine, and is built on the Company’s RespirVec platform technology, which allows rapid and broad activation of innate and long-term adaptive immune responses. Since NasoShield can be administered as an intranasal dose, it is a convenient and simple alternative relative to the only approved vaccine, Emergent BioSolutions’ (NYSE: EBS) injectable Biothrax, and has potential to offer faster and more durable protection against anthrax.

Mechanism of Action

Anthrax vaccines are not designed to inhibit B. anthracis growth, but are instead designed to interfere with Protective Antigen (PA) and disrupt its critical role in exotoxin-mediated pathogenesis. B. anthracis PA protein combines with lethal factor and edema factor to produce dangerous virulence factors called anthrax toxins. Neutralizing antibodies against B. anthracis PA have been shown to protect against anthrax infections in multiple studies.13 NasoShield is a replication-deficient adenovirus serotype 5 (Ad5)-vectored vaccine engineered to encode the B. anthracis PA gene. Similar to Altimmune’s influenza vaccine NasoVAX, intranasal administration of NasoShield mimics natural infection, thus inducing mucosal immunity that may improve the protection against anthrax pathogens entering the host through the upper respiratory tract. Once internalized through the nasal passage, adenovirusmediated expression of B. anthracis PA elicits an adaptive immune response in the host, stimulating the production of neutralizing antibodies for long-term protection against B. anthracis PA. NasoShield’s painless and convenient route of administration offers a significant advantage over the only currently FDA-approved anthrax vaccine, BioThrax, which requires five intramuscular injections over 18 months with additional annual booster shots to maintain immunity.

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12. Research and Markets: Trends and Opportunities Report
13. Little, S.F. et al., 2006. Duration of protection of rabbits after vaccination with Bacillus anthracis recombinant protective antigen vaccine. Vaccine, 24(14), pp.2530–2536.