Eric J Ma's Website

Session 1: New antibiotic strategies and therapeutics:

In this section, scientists and group leaders presented novel ways of thinking about anti-bacterial treatment.

1. Small molecules: focus on how to get molecules into the cell. (Anita Miller, Entasis)
2. Phage lysins: one component of phages, add externally to a bacteria. (Vincent Fischetti, Rockefeller University)
3. Ecobiotics: Consortia of commensal bacteria to restore general diversity, or impact specific pathways. (Matthew Henn, Seres Therapeutics)
4. Chemical discovery: Gene clusters can predict biochemical activity of natural products, great for discovering new chemicals. Cool point I took home - a gene cluster that encodes a molecule that destroys function of a common protein may also encode a resistant version of that version. (Emily Balskus, Harvard University)

Session 2: Creating a sustainable ecosystem for antibiotic production.

In this section, representatives from finance, manufacturing, regulatory, and public policy discussed how they thought a sustainable ecosystem for producing antibiotics could be fostered.

Panel members:

• Joseph Larsen, BARDA
• Cara Cassino, Contrafect
• Edward Cox, FDA
• Alan Carr, Needham & Co.

Are there enough ideas in the pipeline?

• BARDA model: product accelerator; public-private partnerships.
• Missing: a "pull" incentive - if I develop X successfully, I will get paid Y. Need lawmakers’ help.

Are there enough ideas in the pipeline?

• BARDA model: product accelerator; public-private partnerships.
• Missing: a "pull" incentive - if I develop X successfully, I will get paid Y. Need lawmakers’ help.
• There’s a move towards targeted drug therapies.
• New paradigms come with unknown risks.
• Market around antibiotics: there’s underlying interest, but some skepticism and fear towards biotech.
• There are sub-sections of antibiotics space (e.g. gram positives) that can do well, because of unmet need.
• Regulatory: yet, if there’s an unmet need, then we’re behind. Private vs. societal value are not aligned.
• Antibiotics: a bit like fire department. We don’t pay fire department by the number of times they put out fires, but as an insurance. Payments are de-linked from the amount of usage.
• Private sector model isn’t going to foster investment.
• Incentives need to factor in not just pathogens, but also clinical manifestations of the pathogens.

Diagnostics?

• Rapid, within 1-2 hours, which can be good enough to form the basis for decision making, is an unmet need.
• Susceptibility testing is also important.

Why is there not reduced antibiotic usage in agriculture?

• Companies that manufacture these products are told to voluntarily remove indications for non-therapeutic uses.
• By end of year, antibiotics will need to be prescribed by a vet.
• Antibiotics have growth promotion and prophylactic non-therapeutic uses.
• Interestingly: high prices per course discourages lax usage. Interesting…… But what if the economic & regulatory model was changed?

New antibiotics are a bit like the different types of fire extinguishers (one for petrochemical, one for electrical, etc.). You only buy a new fire extinguisher if it is sufficiently different. New antibiotics have to likewise be sufficiently different.

What’s the one thing that has to be done?

• From small antibiotic developer’s perspective: prioritization is needed. Favourable reimbursement is needed. Also support the fire department model, but don’t discriminate between large and small developers.
• Push incentives are helping, but we need the "pull" incentives, i.e. the known return on investment.
• Parallels between rare diseases and antibiotics. "Fire department"-style incentives might be a good way forward.
• Rapid, high resolution diagnostics would be really transformative, for example, in their use in clinical trials for rare infections.
• Clinical trial networks, infrastructure to be able to study new, narrow-spectrum agents.

Session 3: Entrepreneurship

Things to note:

• Make sure the science is solid. Nature cannot be fooled.
  • Regulatory issues must be thought of right from the beginning.
• Technology can come from anywhere. A good company is one that addresses an unmet need.
• Talk with regulatory people early on. They sometimes have productive things to say as well.
• Get a great team together. They should know the market, believe in the mission.
• Focus on proof of concept and differentiation. If these are achieved, good things can happen.
• Talk with people you trust, who are willing to tell you "this idea is a bad idea".

Session 4: Diagnostics

• From talking with others over lunch, I found that diagnostics have to be technically so simple (i.e. solid phase chemistry).
• Clinical goals:
  • Reduce use of antibiotics
  • Rapid diagnosis and treatment
  • Data to guide the most appropriate antibiotic
  • Clinicians need to know when to withhold and when to deploy antibiotics.
• Unmet clinical needs:
  • Rapid, simple, inexpensive to distinguish viral from bacterial infection, or if a person is even infected or not.
    • CLIA-waived - so simple, a non-laboratory person can do it.
    • Likely a biomarker test.
  • Rapid, simple inexpensive test to detect viral pathogens
    • There are simple molecular assays, but none that are inexpensive.
  • Rapid identification of bacteria
    • Laboratory-based test
    • Improvements are being made.
  • Rapid susceptibility testing
    • Still a challenge.
• Rapid: a context-specific term.
  • Bacterial vs. viral: 15-20 minutes.
  • Viral detection: 15-20 minutes, on-demand and not batched.
  • Bacterial detection: an hour or less, on-demand.
  • Susceptibility: < 6 hours.
• Identification of species is better than gram pos/neg.
• T2 Biosystems: an interesting platform, PCR-based detection.
• Resistance testing:
  • Genotypic is helpful for gram-positive strains. Gram-negatives are more challenging.
  • Phenotypic testing: Accelerate Diagnostics and Geneweave. Accelerate uses FISH and growth characteristics.
• How to change a clinician’s practice?
  • Reliable test.
  • Outcomes data - prove to doctor that test makes a difference.
  • Reimbursement model that encourages use of test.
  • Educate physicians - what and when to order, how to interpret results. (Interpretation is key!)
• T2 diagnostics: magnetic resonance-based detection of pathogens.
• What is the best economic model for infectious disease products?