About
Life sciences entrepreneur.
Specialties: Biotech, microbiome, venture creation
Activity
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Concerto's clinical trial, ENS-002 for Atopic Dermatitis in Adults, is now recruiting. The study site is in Austin, TX. If you are interested in…
Concerto's clinical trial, ENS-002 for Atopic Dermatitis in Adults, is now recruiting. The study site is in Austin, TX. If you are interested in…
Liked by Bernat Olle
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Proud to share the Bill & Melinda Gates Foundation's equity investment in Radiant Biotherapeutics's $35 million Series A financing. Radiant's…
Proud to share the Bill & Melinda Gates Foundation's equity investment in Radiant Biotherapeutics's $35 million Series A financing. Radiant's…
Liked by Bernat Olle
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Tremendous that the AMR Action Fund led the most recent investment round in Novo Holdings portfolio company F2G. And btw I had no personal…
Tremendous that the AMR Action Fund led the most recent investment round in Novo Holdings portfolio company F2G. And btw I had no personal…
Liked by Bernat Olle
Experience
Education
Volunteer Experience
Publications
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VE303, a Defined Bacterial Consortium, for Prevention of Recurrent Clostridioides difficile Infection A Randomized Clinical Trial
JAMA
Key Points
Question In adults at high risk for recurrence of Clostridioides difficile infection (CDI), does VE303 (a novel oral microbiome-directed therapy composed of nonpathogenic, nontoxigenic, commensal strains of Clostridia) reduce the likelihood of CDI recurrence?
Findings Through week 8, the CDI recurrence rate (using the most inclusive, combined clinical and laboratory definition of outcome) was 13.8% for the high-dose VE303 group, 37.0% for the low-dose VE303 group, and…Key Points
Question In adults at high risk for recurrence of Clostridioides difficile infection (CDI), does VE303 (a novel oral microbiome-directed therapy composed of nonpathogenic, nontoxigenic, commensal strains of Clostridia) reduce the likelihood of CDI recurrence?
Findings Through week 8, the CDI recurrence rate (using the most inclusive, combined clinical and laboratory definition of outcome) was 13.8% for the high-dose VE303 group, 37.0% for the low-dose VE303 group, and 45.5% for the placebo group.
Meaning High-dose VE303 prevented recurrent CDI compared with placebo. -
Identification of trypsin-degrading commensals in the large intestine
Nature
Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion…
Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.
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Colonization of the live biotherapeutic product VE303 and modulation of the microbiota and metabolites in healthy volunteers.
Cell Host Microbe
Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative…
Manipulation of the gut microbiota via fecal microbiota transplantation (FMT) has shown clinical promise in diseases such as recurrent Clostridioides difficile infection (rCDI). However, the variable nature of this approach makes it challenging to describe the relationship between fecal strain colonization, corresponding microbiota changes, and clinical efficacy. Live biotherapeutic products (LBPs) consisting of defined consortia of clonal bacterial isolates have been proposed as an alternative therapeutic class because of their promising preclinical results and safety profile. We describe VE303, an LBP comprising 8 commensal Clostridia strains under development for rCDI, and its early clinical development in healthy volunteers (HVs). In a phase 1a/b study in HVs, VE303 is determined to be safe and well-tolerated at all doses tested. VE303 strains optimally colonize HVs if dosed over multiple days after vancomycin pretreatment. VE303 promotes the establishment of a microbiota community known to provide colonization resistance.
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Opportunities and Challenges in Development of Live Biotherapeutic Products To Fight Infections
Journal of Infectious Diseases
Treatment of bacterial infections with broad spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic resistant pathogens. Live Biotherapeutic Products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug…
Treatment of bacterial infections with broad spectrum antibiotics is a strategy severely limited by the decreased ability of the perturbed resident microbiota to control expansion of antibiotic resistant pathogens. Live Biotherapeutic Products (LBPs) could provide an alternative to antibiotics in infection control by restoring gut colonization resistance and controlling expansion of resistant strains, an important therapeutic need not being addressed with existing anti-infective drug modalities. We review opportunities and challenges in developing LBPs for MDRO colonization and infection control, with a focus on commercial FMT-like products and defined bacterial consortia, and spanning considerations related to availability of models for rational drug candidate selection and dose regimen selection, GMP manufacturing, intellectual property, and commercial viability.
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A defined commensal consortium elicits CD8 T cells and anti-cancer immunity
Nature
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing…
There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-γ-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103+ dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.
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Translating microbiome futures
Nature Biotechnology
A group of microbiome researchers discuss some of the challenges in developing a new generation of microbiome therapies
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Computer-guided design of optimal microbial consortia for immune system modulation
eLIFE
Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome composition and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (Treg) data from germ-free mice, we…
Manipulation of the gut microbiota holds great promise for the treatment of diseases. However, a major challenge is the identification of therapeutically potent microbial consortia that colonize the host effectively while maximizing immunologic outcome. Here, we propose a novel workflow to select optimal immune-inducing consortia from microbiome composition and immune effectors measurements. Using published and newly generated microbial and regulatory T-cell (Treg) data from germ-free mice, we estimate the contribution of twelve Clostridia strains with known immune-modulating effect to Treg induction. Combining this with a longitudinal data-constrained ecological model, we predict the ability of every attainable and ecologically stable subconsortium in promoting Treg activation and rank them by the Treg Induction Score (TrIS). Experimental validation of selected consortia indicates a strong and statistically significant correlation between predicted TrIS and measured Treg. We argue that computational indexes, such as the TrIS, are valuable tools for the systematic selection of immune-modulating bacteriotherapeutics.
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MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses
Genome Biology
Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE’s utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an…
Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE’s utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations.
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FDA’s pathway for regulation of FMT: not so fraught
Journal of Law and the Biosciences
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Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota
Nature
Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4(+)FOXP3(+) regulatory T (Treg)-cell-inducing…
Manipulation of the gut microbiota holds great promise for the treatment of inflammatory and allergic diseases. Although numerous probiotic microorganisms have been identified, there remains a compelling need to discover organisms that elicit more robust therapeutic responses, are compatible with the host, and can affect a specific arm of the host immune system in a well-controlled, physiological manner. Here we use a rational approach to isolate CD4(+)FOXP3(+) regulatory T (Treg)-cell-inducing bacterial strains from the human indigenous microbiota. Starting with a healthy human faecal sample, a sequence of selection steps was applied to obtain mice colonized with human microbiota enriched in Treg-cell-inducing species. From these mice, we isolated and selected 17 strains of bacteria on the basis of their high potency in enhancing Treg cell abundance and inducing important anti-inflammatory molecules--including interleukin-10 (IL-) and inducible T-cell co-stimulator (ICOS)--in Treg cells upon inoculation into germ-free mice. Genome sequencing revealed that the 17 strains fall within clusters IV, XIVa and XVIII of Clostridia, which lack prominent toxins and virulence factors. The 17 strains act as a community to provide bacterial antigens and a TGF-β-rich environment to help expansion and differentiation of Treg cells. Oral administration of the combination of 17 strains to adult mice attenuated disease in models of colitis and allergic diarrhoea. Use of the isolated strains may allow for tailored therapeutic manipulation of human immune disorders.
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Who Will Figure Out How to Make a Business Out of Fecal Transplants?
FierceBiotech - Industry Voices
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Medicines from microbiota
Nature Biotechnology
Five years after the launch of the Human Microbiome Project, several ventures are seeking to capitalize on the clinical promise of microbiome modulation. Commercialization of drugs that influence the human flora poses some unique scientific, translational and regulatory challenges.
Honors & Awards
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2019 Immigrant Entrepreneur Award, Life Sciences
The Immigrant Learning Center
The Barry M. Portnoy Immigrant Entrepreneur Award from The Immigrant Learning Center honors the outstanding contributions of immigrant entrepreneurs who have built successful businesses in Massachusetts, including their impact on the innovation economy and service to local neighborhoods.
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Pharma Exec Emerging Pharma Leader 2018
Pharmaceutical Executive
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Boston Business Journal’s 2018 40 Under 40 honorees
Boston Business Journal
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Entrepreneur Of The Year®2018 New England Finalist
Ernst & Young
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Vedanta selected to Fierce 15, 2016 class
FierceBiotech
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NEVY 2016 Rising Star Entrepreneur nominee
New England Venture Capital Association
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TR35 - Spain, Innovator of the Year
MIT Technology Review
Selected by MIT Technology Review as Spanish Innovator of the Year under the age of 35 for translational work in development of therapeutics that modulate the human microbiome
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MIT - J Edward Vivian Award
MIT School of Chemical Engineering Practice
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La Caixa fellowship
La Caixa
2-year full scholarship for postgraduate studies abroad
Languages
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Catalan
Native or bilingual proficiency
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Spanish
Native or bilingual proficiency
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English
Native or bilingual proficiency
More activity by Bernat
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Celebrating 3 years at J.P. Morgan Private Bank
Celebrating 3 years at J.P. Morgan Private Bank
Liked by Bernat Olle
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All-In Summit 2024 All-In Podcast I was absolutely thrilled to hear from true leaders this week, moderated by none other than the Besties Jason…
All-In Summit 2024 All-In Podcast I was absolutely thrilled to hear from true leaders this week, moderated by none other than the Besties Jason…
Liked by Bernat Olle
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I had an incredible experience being a part of the growing women's group at the All In Podcast Summit! It was truly inspiring to connect with so many…
I had an incredible experience being a part of the growing women's group at the All In Podcast Summit! It was truly inspiring to connect with so many…
Liked by Bernat Olle
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Gear check: Timmerman Traverse for Sickle Forward is fired up for Kilimanjaro, starting Sept. 11. Thanks to all who contributed to our $1.2 million…
Gear check: Timmerman Traverse for Sickle Forward is fired up for Kilimanjaro, starting Sept. 11. Thanks to all who contributed to our $1.2 million…
Liked by Bernat Olle
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I'm thrilled to be joining the team at Kendall Investor Relations, LLC where we provide senior-level strategic and operational IR services for the…
I'm thrilled to be joining the team at Kendall Investor Relations, LLC where we provide senior-level strategic and operational IR services for the…
Liked by Bernat Olle
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Thrilled to announce I have joined Spencer Stuart as a member of the firm’s Biopharma Practice! I’m looking forward to reconnecting and continuing…
Thrilled to announce I have joined Spencer Stuart as a member of the firm’s Biopharma Practice! I’m looking forward to reconnecting and continuing…
Liked by Bernat Olle
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Bernat Olle
Bat en si
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