Focus

Appili Therapeutics, Inc. was specifically founded to advance the global fight against infectious disease by matching clearly-defined medical needs with drug development programs and funding mechanisms that allow the company to accelerate the availability of improved anti-infective solutions or produce entirely novel agents.

The Appili team follows a rigorous process to identify and evaluate drug development opportunities, and to ensure that they align optimally with market need. Because the company is not bound to a specific technology or platform, the team is able to consider a wide range of additions to its pipeline, and target programs that rapidly generate value or, in time, represent significant advances in the treatment of infectious diseases.

This flexibility also allows Appili to pursue development opportunities that provide access to non-dilutive funding from government incentive programs or industry partnerships. An important aspect of this approach to portfolio building is discipline – Appili’s team has reviewed and passed on over 100 drug development projects that did not meet its scientific, clinical, patient-care and financial criteria.

In response to the global threat of increasingly resistant or difficult-to-treat infectious diseases, federal agencies have created a number of special programs and incentives to encourage the development of new anti-infectives.

GenericImage

Recent regulatory changes have incentivized the development of anti-infective agents to increase commercialization:

The Generating Antibiotics Incentives Now (GAIN) Act enacted in 2012 and the 21st Century Cures Act enacted in 2016 both introduced new streamlined processes for expedited antibiotic development and review by the FDA.  The GAIN Act also outlines a mechanism granting eligible anti-infecives an additional five years of market exclusivity.

The Priority Review Voucher Program is an incentive for companies to invest in new drugs for underserved patient populations through the award of a transferable “priority review vouchers.” A Priority Review Voucher can be applied to any drug development program, and typically reduces the time for the FDA to review a new drug application to as little as six months.  Novel agents for the treatment of neglected tropical diseases including malaria, tuberculosis, and leishmaniasis are voucher eligible.  In addition, the Priority Review Voucher program was expanded in 2016 to address gaps in medical countermeasure development.  New vaccines and therapies targeting major biodefense threats such as anthrax, tularemia, and smallpox are now eligible to receive a voucher.

The Generating Antibiotics Incentives Now (GAIN) Act, which came into effect on October 1, 2012, provides a favorable environment for the development of new antibiotics. Under the GAIN Act, a qualified infectious disease product (QIDP) is a new “antibacterial or antifungal drug for human use intended to treat serious or life-threatening infections, including those caused by an antibacterial or antifungal resistant pathogen, including novel or emerging infectious pathogens.” Under the Act, sponsors developing QIDPs may benefit from the following incentives:

  1. Market exclusivity. QIDPs would be issued five years of market exclusivity in addition to the periods of exclusivity for which they would otherwise qualify. In the US, new small molecule drugs are granted five years of Hatch Waxman market exclusivity, so this provision would provide a total of ten years of market exclusivity regardless of patent position.
  2. Priority review. QIDPs would qualify for Priority Review by the FDA, which would cut the time to approval to six months.
  3. Fast track review. Sponsors of QIDPs would be provided with early and frequent communications with the FDA, in addition to the typical review opportunities.
  4. Updated guidance. The GAIN Act provides a specific timetable for the FDA to develop and issue final guidance on how to conduct antibiotics trials.
  5. Pathogen focused drug development. The FDA will issue guidance on pathogen-focused antibacterial drug development rather than disease-focused development that currently exists.

The 21st Century Cures Act, signed into law in December 2016, has provided additional regulatory incentives to promote the development of innovative infectious disease therapies and vaccines.  The Act expands the Priority Review Voucher program to include medical countermeasures for biodefense pathogens and also introduces the Limited Population Antibacterial (LPAD) regulatory pathway.  The LPAD pathway is intended to promote the development of therapies for multidrug-resistant pathogens.  Recognizing that patients with multidrug-resistant infections are rare and large-scale clinical trials are not feasible, the LPAD will allow for smaller clinical trials and increased reliance on preclinical data to support approval.  The LPAD provides innovator companies with an additional pathway for streamlined antibiotic development distinct from the pathogen focused development pathway outlined in the GAIN Act.

Priority Review Vouchers (PRV) came into effect in 2007, with the first voucher issued in 2009. Under the initial law, a developer of a treatment for a neglected or rare pediatric disease receives a voucher for priority review from the FDA to be used with a product of its choice.  In 2016, the 21st Century Cures Act expanded the list of voucher eligible programs to include therapies and vaccines for biodefense priority pathogens.

PRVs may also be sold to other pharmaceutical companies to improve the return on investment in areas of drug development that previously struggled from a lack of innovation due to more challenging markets. Vouchers are typically sold for values well in excess of $100M:

  • 2014
    • BioMarin to Sanofi / Regeneron: $67.5M
    • Knight Therapeutics to Gilead: $125M
  • 2015
    • Asklepion / Retrophin to Sanofi: $245M
    • United Therapeutics to AbbVie: $350M
  • 2016
    • PaxVax to Gilead: $200M
  • 2017
    • Sarepta Therapeutics to Gilead: $125M
    • Ultragenyx to Novartis: $130M