PeptiShield

PeptiShield seeks to develop antimicrobial peptides as a novel class of antibiotics to combat growing resistance. By researching synergistic peptide combinations, optimizing delivery methods, and advancing candidates through approval/trials, our solution aims to revolutionize infection treatment and strengthen global defenses against antimicrobial resistance.

The Team Lead for PeptiShield is Dr. Ansila Emmanuel, MD, who serves as Director of the Antimicrobial Resistance Research Program at Muhumbili Medical Research Centre in Dar es Salaam, Tanzania.

The growing global crisis of antimicrobial resistance poses a grave threat in Tanzania and Sub-Saharan Africa. According to the WHO, at least 140,000 neonatal sepsis deaths occur annually in Sub-Saharan Africa due to drug-resistant bacteria. In Tanzania, a national AMR action plan found multidrug-resistant bacteria were present in over 60% of hospital samples tested, with limited treatment options remaining. 

A major driver perpetuating the problem is overuse and misuse of antibiotics. In Tanzania, antibiotics can be purchased over the counter without a prescription. Without medical guidance on appropriate dosage and duration, misuse runs rampant. Substandard and falsified medicines flooding markets also undermine effective treatment. These problems disproportionately impact vulnerable communities in Tanzania and globally.

If left unaddressed, antibiotic resistance will seriously undermine development gains in the region. It is estimated that antimicrobial resistance could displace over 24 million people into extreme poverty by 2030. The agricultural sector, hugely important to Tanzania's economy, is also threatened. Without effective antibiotics, common bacterial infections can spread rapidly through livestock and crops. This poses risks to food security and livelihoods. 

PeptiShield directly addresses causes perpetuating this growing crisis through developing an innovative new class of antibiotics - antimicrobial peptides.

PeptiShield primarily aims to serve the estimated 100,000 patients in Tanzania each year who contract antibiotic-resistant bacterial infections. This number is expected to rise sharply without new treatment alternatives.

We are also supporting the over 3000 healthcare providers across Tanzania who are on the frontlines combating resistance. In surveys of doctors and nurses at our collaborating hospitals, 98% said they felt limited by the lack of effective drugs for resistant infections. PeptiShield seeks to address this urgent unmet need. 

To understand the patient experience, we conducted in-depth interviews with 50 individuals or their families directly impacted by drug-resistant infections. Alarmingly, 12 reported losing family members and 36 detailed severe financial and emotional hardships. 

As part of our ongoing engagement efforts, we have worked with community leaders to establish four local advisory boards with over 75 members representing all regions of Tanzania. Through their guidance and prioritization of health issues, we have been able to refine our research focus on the pathogens and resistant profiles of greatest local concern. Going forward, we will leverage these advisory boards to help advance our therapies and ensure maximum patient benefit and accessibility.

PeptiShield provides four key public goods:

1. Open-access data: We maintain an openly accessible database cataloging all newly discovered AMP sequences from Tanzanian organisms. This expands scientific understanding of natural antimicrobial solutions.

2. Peer-reviewed research: All discovery and development work will be documented through open publication to advance global knowledge in this critical healthcare area. 

3. Community access: Approved therapies developed will be provided to Tanzanian patients at the lowest possible cost through cooperation with public health networks to maximize accessibility.

4. Capacity building: We mentor local students and researchers to help establish African research leadership in AMR and health technology development through training partnerships with Tanzanian institutions. This aims to strengthen in-country expertise over the long run.

By prioritizing open data sharing, documentation of research and results, community delivery models, and building local skills, PeptiShield is designed from the start to generate public goods that outlive the project through empowering the healthcare system and research community globally in the fight against drug resistance.

Our solution will create tangible impact for patients and communities in Tanzania in the following ways:

Activities: PeptiShield aims to discover 2+ novel AMPs per monthr and progress at least one optimized combination therapy through clinical trials by 2026. 

Outputs: This will generate new treatment options evaluated using clinical and economic outcomes data from Tanzanian trials. 

Short-term outcomes: More effective and affordable therapies implemented through public health networks will improve clinical cure rates for resistant infections from <50% to >80% within 3 years for our target population of 100,000+ annual patients.

Intermediate outcomes: Lower health costs and productivity losses per patient will save the Tanzanian economy over $10 million annually according to our economic model validated by local healthcare researchers. 

Long-term impacts: Wider availability of alternative treatments will curb growth rates of resistant pathogens, reducing the 5-10 year mortality impact of "superbugs" on underserved rural populations which bear the highest burden.

Overall, PeptiShield aims to concretely improve clinical outcomes, lower costs, and slow AMR trends - creating sustained population health benefits in Tanzania through our made-in-Africa solutions.

Over the next year, PeptiShield aims to:

- Discover 10+ novel AMP sequences through profiling Tanzanian microbiomes/biodiversity. 

- Optimize top 2 candidate peptides into therapeutic combinations through microfluidic assays.

- Complete animal efficacy/toxicity testing for lead mixtures. 

Within 3 years, we will:

- Double our rate of AMP discovery to 2+ per month through expanded field sampling.

- Progress lead mixtures through preclinical development including pharmacokinetics, manufacturing scale-up with industry partners. 

- Launch first-in-human Phase 1 safety trials on optimized top therapies.

- Establish a sustainable pipeline of combo therapies in development facilitated by our discovery platform and integrated data. 

- Engage 10+ regional healthcare facilities for epidemiological monitoring and future efficacy trials.

- Build in-country R&D capacity through a new Tanzanian center training 100+ African researchers.

By aggressively progressing candidates, sustaining discovery innovation, and empowering local partners - we aim to continuously deliver a growing portfolio of viable treatment alternatives Transforming AMR management in Tanzania and building African leadership in this domain globally over the long-term.

We have established the following key performance indicators (KPIs) to measure PeptiShield's success:

1. Novel AMP discovery rate - Benchmark is 2 novel candidates/year identified through genomic/proteomic analyses. Currently achieving 1 sequence/month. 

2. In vitro activity - Candidates must demonstrate >90% killing of resistant clinical isolates in microfluidic screening within 48hrs. Lead mixtures show 100% eradication at 1/100th individual doses.

3. Animal model efficacy - Treatments must resolve lung infection symptoms in >80% of mice compared to <50% for controls, within 5 days as measured by microCT imaging. Current leads meet this endpoint.

4. Clinical impact - Once in human trials, therapies must achieve >70% clinical cure rates, defined as symptom resolution sustained 30 days post-treatment based on WHO guidelines. 

5. Epidemiological impact - Over 5 years, reduce drug resistance levels among common pathogens like Pseudomonas by >15% and associated mortality in Tanzania by >10% per UN AMR targets.

We regularly evaluate performance against these KPIs that span our pipeline from discovery to population health impact. External expert review also validates our approach and progress in delivering on AMR solutions for Tanzania.

The key barriers PeptiShield faces and our plans to overcome them are:

Financial: Securing seed funding is critical but challenging in Tanzania. We will pursue regional grants and impact investors who recognize our potential. 

Policy: Navigating clinical trial approvals takes time. We will engage the Tanzanian Food and Drug Authority early through educational workshops on our novel approach. 

Infrastructure: Limited research facilities constrain work. Partnering with established Tanzanian universities gives us lab access while mentoring their students.

Capacity: Developing local expertise requires sustained training. Beyond training programs, we create long-term roles for former trainees within PeptiShield operations.

Collaboration: Multi-sector partnerships are needed but trust takes time. We earn credibility through open data/results sharing and prioritizing local health progress over commercialization. 

Market forces: New drugs face adoption barriers. Close partnerships with Tanzanian hospitals and endorsement of therapies through nationwide guidelines pave the path for uptake by the public system reaching underserved communities.

By proactively planning for financial viability, engaging with regulators, investing in local capacity and collaboration through trust-building - we aim to systematically reduce barriers to deliver on our vision of resistant infection solutions developed and distributed sustainably within Tanzania.

We are applying to The Trinity Challenge because its goals of developing transformational solutions to critical global issues closely aligns with PeptiShield's mission of combating antimicrobial resistance in Africa. 

The key barriers the Challenge can help us overcome include:

Funding - As an early stage non-profit, securing initial seed capital is our primary challenge holding back technical progress. £1 million from the Challenge would remove this funding barrier allowing meaningful multi-year work. 

Capacity Building - Resources from the Challenge would develop in-country infrastructure like our proposed Tanzanian research center, along with training African scientists - directly growing expertise to sustain indigenous solution-development long term. 

Scaling Impact - Reaching more Tanzanians requires scaled clinical validation and deployment supported by Challenge funding. Its substantial rewards incentivize ambitious goals like introducing our first therapies and epidemiological monitoring networks to maximize health impact.

Partnerships - Association with a prestigious program like the Challenge boosts credibility, opening doors to complementary partners that can help our mission but have been reluctant without demonstration of significant backing and achievement.

Based on the expertise and resources offered, there are three key organizations we would aim to collaborate with to support scaling our solution:

1. Wellcome - as the anchor funder of this Challenge, Wellcome's network and experience developing initiatives against AMR would be hugely beneficial. Their support could help advance our clinical validation plans. 

2. Amazon Web Services - AWS' computing infrastructure and advisory services could help optimize our bioinformatics platform and discovery processes. Collaborating with AWS also opens opportunities to deploy our solutions at scale.  

3. British Society of Antimicrobial Chemotherapy - BSAC is uniquely positioned to help expand our networks of clinicians and researchers contributing data insights. Their guidance on regulatory pathways and involvement in policy discussions would strengthen our impact.

Working closely with these organizations would help accelerate our timeline by leveraging their complementary expertise across funding, technology and stakeholder engagement. Importantly, collaborating primarily with UK and Africa-focused partners ensures the utmost cultural sensitivity and potential for long-term sustainability of solutions in Tanzania.