On May 14, 2020, a team spanning the University of California San Diego, San Francisco General Hospital, Cook County Health and Hospitals System in Chicago, and Washington University in St. Louis published a milestone study in the New England Journal of Medicine. Cohen et al demonstrated the effectiveness of LACTIN-V, a new Live Biotherapeutic Product (LBP) created by Osel, Inc. for the treatment of bacterial vaginosis (BV).
LACTIN-V is a single-strain, topically-administered LBP containing Lactobacillus crispatus CTV-05, a protective human vaginal bacterium that helps to combat the pathogenic bacteria and dysbiosis observed in recurrent BV and urinary tract infections. Its success marks the first single-strain LBP to show clinically significant efficacy in a randomized, double-blind, placebo-controlled Phase 2b trial in the US.
The study was supported by grants from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). List Labs is excited by this landmark discovery, by the prospects of this discovery for women’s health around the world, and for further supporting the use of LBPs as a viable therapeutic. We had a chat with Osel’s Director of Product Development, Tom Parks, to find out more about the project, it’s challenges, and why the product is successful:
What are dysbiosis and BV?
Dysbiosis is a disruption of the human microbiome: the collection of microorganisms, including bacteria, that naturally live on and in our bodies. The full function of the microbiome isn’t fully understood, but dysbiosis is known to be involved in a wide range of skin disorders, intestinal problems and gum diseases, among many others.
Bacterial vaginosis is an ecological disorder of the vaginal microbiota in which hydrogen peroxide-producing lactobacilli are displaced by predominantly anaerobic bacteria (e.g. Prevotella and Mobiluncus species), Gardnerella vaginalis, and Atopium vaginae. It is the most common vaginal infection worldwide among women of reproductive age, and affects about 30% of women in the US. Treatment usually consists of a course of an antibiotic such as metronidazole lasting about five days. The treatment itself is usually effective, but in about 75% of cases BV returns within a year, often within just a few weeks.
Why is treating BV so challenging?
The tendency of BV to recur is due to failure to re-establish a Lactobacillus-dominated vaginal microbiome. Since the only treatment is another course of metronidazole or a similar antibiotic, this can lead to a cycle of re-infection. In addition to the discomfort and negative impact on the quality of life, BV is a risk factor for a wide range of sexually transmitted infections, including HIV/AIDS. It is also a risk factor for premature birth and other reproductive health complications.
Currently there is no approved treatment to prevent the recurrence of BV. Women have tried a range of home remedies, from yogurt to tea tree oil. As might be expected, these are often ineffective, and may have side effects of their own.
Osel has developed a treatment for BV that breaks the cycle of dysbiosis. LACTIN-V is a live biotherapeutic product (LBP) containing the hydrogen peroxide-producing strain Lactobacillus crispatus CTV-05, which is a protective member of the native microbiome. Administered after the normal course of antibiotics (once a day for five days, and then twice a week for 10 weeks), LACTIN-V helps to restore the normal vaginal environment and prevent re-emergence of the organisms that cause BV. In the study reported in NEJM, BV recurrence was significantly less in women treated with Lactin-V (30%) compared to the placebo group (45%) (P=0.01).
What goes into manufacturing an LBP?
An LBP is a therapeutic agent based around a live microorganism, intended to restore a balance in the microbiome disrupted by a disease condition. A contract development and manufacturing organization (CDMO) can provide essential expertise for developing an LBP, but finding the right CDMO is tricky since many contract manufacturing organizations do not have experience with maintaining viability of the microorganism through the entire manufacturing process or are flexible for the process nuances of an LBP product. In addition, many organisms of interest as LBPs are anaerobic to some extent (for example, Lactobacillus are facultative anaerobes), and/or spore-forming. Working with such organisms takes special expertise and facilities to provide necessary containment and segregation, maintain viability, maximize yield, and avoid pitfalls.
Osel’s Tom Parks explains, “Relevant live biologic product experience and GMP manufacturing capabilities are obviously important. Flexibility to handle a number of product formats is also helpful. Since the field is relatively new, companies that manufacture LBPs are few and far between.”
Are you looking for a CDMO for your LBP project? List Labs has 40 years of experience manufacturing bacterial products and many different LBP products for Phase 1 and 2 clinical trials for indications in the gut, skin, vaginal mucosa, and CNS. List Labs has the expertise for handling and cultivating anaerobic bacteria and spore formers. We are uniquely qualified to provide insight and the flexibility to match the needs and requirements of each individual project, such as filling different product formats. We are a passionate and dedicated partner who works as an extension of your team to ensure the success of your project. If you are interested in an LBP project, contact us at email@example.com
By: Rachel Berlin, Marketing Manager
Microbiome research is uncovering the enormous potential for developing drugs, such a live biotherapeutic products, from the microbiome. This burgeoning field is the future of medicine.
List Labs is excited and proud to support microbiome research by providing reagents to scientists studying the human microbiome. Below is a list of microbiome research studies that have used List Labs’ research reagents such as Athrax, Pertussis, Cholera and Difficile Toxins.
List Labs is proud to be exhibiting at the Microbiome Drug Develoment Summit 2018 in Boston, MA. The conference will be held at the Boston Seaport World Trade Center from June 20-22. This conference provides access to the latest preclinical, clinical and commercial case studies from the brightest minds in biopharma and academia to turn microbiome discoveries into patient therapies.
Contact us to schedule a meeting with us at the show to discuss your next project!
By: Rachel Berlin, Marketing Manager
1978 was a great year for scientific advancement – NASA hired the first women astronauts, the first test tube baby was born and List Labs was founded. Linda Shoer, our founder, saw an opportunity when she realized there was a need for a commercial supplier of Cholera Toxin for studies in signal transduction and neuronal track tracing. On May 18, 1978, Linda started something more than a company, she started a family- the List Labs family.
List Labs carries on the values instilled by Linda Shoer and continues to grow our team, our capabilities and experience. We are excited to see what the next 40 years bring!
By: Stacy Burns-Guydish, Ph.D., Senior Director, Production
The terms “Microbiome” and “live biotherapeutics” have been repeated frequently in the last few years in scientific circles. Researchers are understanding more and more about the various microbiomes in the human body and how they affect our overall health. From this research, microorganisms have been identified that may be beneficial to our health and could be used as a therapeutic, otherwise known as a live biotherapeutic products. This article explains an overview of some microbiome and live biotherapeutics basics.
What is Microbiome?
The human microbiome is the collection of trillions of microbes living in and on the human body. Scientists believe that it plays a role in many basic life processes and are important to our health. Perturbation of the microbiome has been associated with a growing number of diseases including inflammatory bowel disease, allergies, asthma, autism, and cancer.
What are some different types of human microbiomes?
Microbiomes are found, for example, in our gut, skin, vagina, and mouth. Each of these sites have a different consortia of microorganisms. Beneficial microorganisms have been identified in each of these niches. Researchers are studying the various human microbiomes to better understand their importance in health and disease.
What is a Live Biotherapeutic Product (LBP)?
A live biotherapeutic product contains a live microorganism that is used for the prevention, treatment, or cure of a disease or condition. As the characterization of the human microbiome and its link to human health has become better understood, microorganisms have been identified which may have a health benefit. The use of these microorganisms as a live biotherapeutic product in clinical application shows great promise. Several clinical trials are underway to evaluate their potential as a therapeutic.
What equipment and facilities are necessary for the production of a Live Biotherapeutic Products?
Many of the microorganisms identified for the manufacture of live biotherapeutic products are obligate or strict anaerobes and spore forming organisms. These type of organisms present unique challenges to the emerging microbiome therapeutic space. In particular, many of the microorganisms are anaerobes which cannot be exposed to air and thus expertise is required in handling and cultivating the organism. Facilities and equipment important for the cGMP manufacturing of these organisms include:
Biological safety cabinets
Anaerobic work stations with internal HEPA filtration for aseptic, anaerobic fill capability
Equipment to scale the process cultivation
Stainless steel or single use bioreactors
Closed harvest systems such as tangential flow filtration with hollow fiber membranes
Semi-automated or automated filling equipment
Freeze drying equipment, i.e. Lyophilizer
Homogenization and milling equipment
List Labs is your partner for Live Biotherapeutic Products
List Labs has manufactured several live biotherapeutic products for phase clinical trials. With 40 years of experience, List Labs is distinctly qualified to help you with your next microbiome project and affords the flexibility required to achieve the strictest timelines and goals. We understand that each project is unique and we draw from our vast experience to deliver you a custom solution that meets your needs. Contact us today to find out how we can help you!
List Labs has extensive experience with microbiome and more specifically live biotherapeutic projects including vaginal, gut, skin and the central nervous system indication and tumor treatment – many of which have completed Phase I and Phase II trials. Stop by our booth and find out how we can help you with your next microbiome project. Learn about how scientists have used List Labs’ products for their microbiome research on our citations page.
Interested in scheduling a meeting with us during the conference? Contact us!
The human body is home to a vast ecosystem of microbes, called the microbiome. Research is shedding light on the importance of the microbiome as a benefactor to our health and development. Perturbation of the microbiome has been associated with a growing number of diseases including inflammatory bowel disease, allergies, asthma, autism, and cancer.
Microbiome Bacteria as Potential Therapy
Commensal bacteria of the microbiome are thought to be potential therapies for prevention or treatment of infections such as Clostridium difficile, acne, and bacterial vaginosis. Live biotherapeutic products (LBP) manufactured from commensal bacteria are being investigated by many companies and several clinical trials are underway.
Anaerobic Cultivation & Containment Required for Microbiome Research
Many of these commensal microorganisms for the manufacture of LBP are obligate or strict anaerobes and spore forming organisms, presenting unique challenges to the emerging microbiome therapeutic space. Expertise and proper equipment for anaerobic cultivation and proper containment of spore forming organisms is lacking in the industry and only a handful of contract manufacturing companies have the capabilities to perform GMP manufacturing anaerobic organisms, creating a bottleneck.
An alternative for companies is to build their own GMP facility, as Seres Therapeutics has done. But start-ups typically do not have the funds to build their own facilities thus the CMO backlog impacts timelines. Most CMO’s quote a wait of 9-12 months for projects to begin. So how will these burgeoning companies meet their aggressive timelines to produce their LBP for clinical trials?
Questions to Ask Partner GMP Labs
If you are a startup, sound advice is to start conversations now with potential CMOs and find out if their capabilities align with your organism cultivation requirements and specifications.
How many Live Biotherapeutic Products have they produced and released?
List Labs Is well suited to Partner in GMP Microbiome Research
List Biological Laboratories, a boutique contract manufacturing company, has the expertise and infrastructure for manufacturing both obligate and strict anaerobes and spore forming organisms. List has over 30 years’ experience cultivating anaerobic organisms. We have produced master and working cell banks and LBP for several customers currently in Phase 1 and 2 clinical trials. In addition, we have expertise in the development of the non-trivial required purity/bioburden assays, including USP61 and UPS62, for testing and release of these unique live microorganism products.
Debra Booth, VP of Operations
Linda Eaton, Ph.D., VP of Research & Development
Stacy Burns-Guydish, Ph.D., Senior Director of Microbiology
PJ Nehil, Sales & Distribution Coordinator
Dear Researchers Everywhere,
List Labs recently exhibited at the 2016 BIO International Convention. As a producer of bacterial products for research, as well as a provider of custom laboratory services, we were excited to meet with current and potential customers. We were eager to gain some insight into the current and future state of biotechnology and the up and coming field of microbiome research. But you never know exactly how you’ll feel until you spend the time in the conference exhibit hall. We were very pleased to see that we are a part of an industry that is moving forward at the pace of a start up, fueled by the novel ideas and intellect of many scientists.
Last week, thousands of people filled the Moscone Convention Center in San Francisco. The event was brilliantly organized and the venue was strategically arranged. The various pavilions were organized by state or country and some by specialty. It was a great opportunity to network and identify new sources for projects and services. Attendees were CEO and business development folks interested in learning more about what exhibitors have to provide. At our booth, we talked about immunotherapy, live biotherapeutics, contract manufacturing, GMP production, and more. It was a pleasure to shake hands with many customers, distributors, and colleagues and discuss ways we can partner with them to move their research forward.
We also had the opportunity to meet with vendors, in shipping, supplies and services. These vendors are critical to delivery of our biological and therapeutic products, and we benefited from learning about their new offerings as strategic partners. The enthusiasm was palpable from both exhibitors and attendees. At this event, we didn’t just meet industry veterans. We met many young scientists and job seekers looking for their first break. Some even came directly to us to hand-deliver their resumes. The event had a job expo, fueling another layer of energy and opportunity for exhibitors. We were resident in the California Pavilion where we learned that the State of California has a Biosciences Training Program, which will help companies pay for new employment training. Community colleges around the country are encouraging students to contribute to the future of biotechnology through clinical and regulatory apprenticeships. It’s great to see that science is providing opportunity for students in so many ways.
In closing, we found the 2016 BIO International Convention to be highly productive for our company. For those of you who didn’t get a chance to meet us at the convention, it’s very easy to reach us online and on social media. We would love to connect with you on LinkedIn, tweet with you on Twitter, like each other on Facebook and Google+. You can also check these accounts if you’re curious about your next opportunity to meet us at a conference. We even have a YouTube channel and a blog where you can learn more about us. We’d love to see your YouTube videos and read your blog if you have them as well. The future of biotechnology looks bright and we’re more excited than ever to be a part of it. We will definitely attend more events like this and we hope to see you at BIO 2017 in San Diego!
Debra, Linda, Stacy, & PJ
Dr. Karen Crawford, President of List Biological Laboratories, Inc.
If you will be in attendance, stop by the List Labs booth and chat with Karen Crawford about your research in the microbiome area. Karen is the president of List Labs and would enjoy speaking with you about our areas of expertise and how we would be able to support your microbiome or live biotherapeutic product work. We love hearing what companies are developing and finding ways to help.
If you want to learn more about our capabilities, check out our website or one of our videos and let us know how we can help you better position yourself to meet your research goals and objectives.