Microbiome Report for Week Ending 4/13/19

MaaT Pharma Announces Second Positive DSMB Safety Assessment of Ph II Study in Acute GvHD
MaaT Pharma announced on 4/9/19 that the independent Data and Safety Monitoring Board (DSMB) recommended the continuation, without amendment, of the ongoing Phase II HERACLES study (NCT03359980). The HERACLES trial investigates the use of lead biotherapeutic MaaT013 in steroid-resistant, gastrointestinal-predominant, acute Graft-versus-Host-Disease (SR GI aGvHD) after allogeneic Hematopoietic Stem-Cell Transplantation (allo-HSCT). The second review assessed the safety of MaaT013 after 10 patients treated, reinforcing the absence of safety issues during the trial as confirmed after the first review. Enrollment of patients in the trial continues as planned with additional sites recently opened in Germany and Italy. As of today a total of 13 patients have been treated in the protocol.

“The high mortality rate of up to 80% after 6 months in gastrointestinal-predominant aGvHD poses a significant unmet medical need and we believe that MaaT013 will improve these patients’ outcomes through a differentiated approach of restoring their immune homeostasis,”
"The relevance of the microbiome in hemato-oncological diseases is increasingly recognized by the medical community and our mission is to develop the first, safe microbiome-based product to help patients with no other options. We look forward to communicating the top-line data of this trial later this year.”

commented Hervé AffagardCo-founder and CEO of MaaT Pharma.
MaaT013 is the first full-ecosystem, off-the-shelf, reproducible, enema formulation manufactured using MaaT Pharma’s integrated Microbiome Restoration Biotherapeutic (MMRB) platform. The product has a stability of up to 24 months and is characterized by a high diversity and consistent richness of microbial species derived from pooled healthy donors and manufactured at the company’s centralized European cGMP production facility. MaaT013 has been granted Orphan Drug Designation by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and is already being administered in compassionate use.

FORTUNE and Great Place to Work Name Second Genome a "Top 10 Best Workplace in Biopharma"
On 4/10/19 Second Genome Announced that FORTUNE and Great Place to Work have honored Second Genome as one of the 2019 Top 10 Best Workplaces in Biopharma. The ranking considered feedback representing almost 730,000 employees working at Great Place to Work-Certified organizations in the health care and biopharma industry. Great Place to Work, a global people analytics and consulting firm, evaluated more than 60 elements of team members' experience on the job. These included the extent to which employees trust leaders, the respect with which people are treated, the fairness of workplace decisions, and how much camaraderie there is among the team. Rankings are based on employees' feedback and reward companies who best include all employees, no matter who they are or what they do for the organization.
"We are thrilled that our employees placed us in the top 10 biopharmaceutical companies within the United States," said Karim Dabbagh, Ph.D., CEO of Second Genome. "Strong cultures lead to business success. The more empowered our employees feel, the bigger impact they have on our mission: to develop proprietary, first-in-class compounds inspired by the microbiome for patients with cancer, gastrointestinal diseases and other disorders."
Second Genome placed 10 on the list, with the full list below:
1. AbbVie
2. United Therapeutics Corporation
3. Horizon Pharma plc
4. Regeneron Pharmaceuticals, Inc.
5. Genentech
6. Novo Nordisk Inc.
7. Tec Laboratories, Inc.
8. Takeda Pharmaceuticals
9. Merck
10. Second Genome

Priobiotic Derived SkinBiotix Shows Efficacy in Increasing Skin Hydration
SkinBioTherapeutics plc (AIM: SBTX), a life science company focused on skin health, Provided  the results of its first human study on 4/8/19.
The study was primarily undertaken to show the effects of SkinBiotix® on the barrier of healthy skin. An important secondary endpoint was to show that the technology is safe and well tolerated in a large group of people (129) using it twice a day for an extended period of time (29 days).
The results of this independent study demonstrate that SkinBiotix® is safe, well tolerated and has efficacy in certain age groups and time points.
The study design involved three groups:
Group 1 applied the active (cream containing SkinBiotix®) to one leg and nothing to the other
Group 2 applied the vehicle (cream containing no SkinBiotix®) to one leg and nothing to the other
Group 3 applied the vehicle to one leg and active to the other.
Measures of the barrier were then performed in all groups at 15 days and 29 days. The primary measures were Corneometry – a measure of how hydrated the skin is, and Transepidermal water loss  (“TEWL”) -a measure of water loss from the skin. A change to the barrier might be expected to be reflected in an increase in skin hydration or a reduction in TEWL. Some additional measurements of skin elasticity were also taken.
Our data showed:
None of the 129 volunteers experienced any adverse skin reactions to the active.
2)      A statistically significant increase in skin hydration at day 15 with the active, which was  better than that produced by the vehicle. This effect was seen in the group under 50 years old. At day 29 there was no difference in skin hydration between any of the groups.
3)      A small but statistically significant decrease in TEWL with the active at day 29 in the group over 60 years old.
4)      In other age groups and also in measures of skin elasticity there was no difference between the vehicle and the active.
The results of this independent study demonstrate that SkinBiotix® is safe, well tolerated and has efficacy in certain age groups and time points. The change in skin hydration and water loss are in line with our expectations from laboratory studies which have shown that SkinBiotix® increases the levels of proteins within the skin that are crucial for a healthy barrier. The increase in skin hydration in the younger group at day 15 may reflect the ability of younger skin to respond to the SkinBiotix® faster than older skin.
Dr Cath O’Neill, CEO of SkinBioTherapeutics, said:
“We are really pleased by these data. To show efficacy at this stage of development  is very exciting since  there is a lot of scope for us to further optimise the formulation, potentially altering the dose of the SkinBiotix® to make it more suitable for different age groups.
It is very difficult to change a healthy barrier and therefore the data showing improvement in some age groups gives us confidence in our partner discussions, and in seeking to develop future applications in disease conditions where the barrier is known to be poor such as eczema”.

Azitra Demonstrates Feasibility of Using the Skin Microbiome to Treat Skin Conditions
On 4/8/19 researchers from Azitra, Inc., in collaboration with independent, nonprofit biomedical research institutionThe Jackson Laboratory (JAX), announced they have demonstrated the feasibility of engineering a commensal bacterium to deliver a key therapeutic protein to the skin. Azitra will be presenting results from the joint research showing the successful genetic engineering of the common skin bacterium, Staphylococcus epidermidis, to produce high levels of functional LEKTI protein, a protease inhibitor involved in regulating the rate of skin loss. The company has designated the engineered LEKTI-expressing S. epidermidis strain as AZT-02, and the research team, including Julia Oh, Ph.D., a skin microbiome expert at JAX has also shown that engineered S. epidermidis efficiently colonizes skin in both wild type mice and in a mouse model of broken skin. Applied topically, AZT-02 offers the prospect for continuous and cost-effective delivery of functional LEKTI to the skin offering the potential to treat the severe genetic skin disease Netherton syndrome(NS).

The new research will be presented on April 10 byTravis Whitfill, MPH, founder and Chief Scientific Officer of Azitra as an oral presentation entitled, “Engineering the Microbiome to Treat Netherton Syndrome, a Rare Skin Disease” at the Keystone Symposia on Skin Health and Disease, held from April 8-11, 2019in Hannover, Germany.

S.epidermidisis a normal constituent of the skin microbiome, and on its own has been shown to help maintain healthy skin by improving the water and lipid content of the skin, decreasing inflammation, promoting tissue repair, and suppressing the levels of undesirable bacteria, including Staphylococcus aureus. Azitra’s core technology combines these characteristics of S. epidermidis with the added ability of delivering therapeutic proteins to the skin. This dual action aims to correct underlying skin defects and address the challenges of dysbiosis to treat complicated skin diseases.

 “Azitra has developed a proprietary strain ofS. epidermidis  with an aim of using this bacterium as a platform for the treatment of skin diseases,” said Mr. Whitfill.“While this organism has the potential for use on its own to help maintain skin health, we are also developing it to serve as a unique delivery system for the cost-efficient production and topical delivery of important therapeutic proteins. These proteins are targeted to treat serious skin disorders. The work presented today clearly demonstrates the feasibility of this approach for the efficient, topical delivery of LEKTI to the skin. The strain, AZT-02,has the potential to be used as a treatment for Netherton syndrome, which is a rare genetic skin disease with no available treatment options.”

NSis a genetic disorder affecting 1 in 200,000 children,caused by mutations in the SPINK5 gene that is responsible for making the LEKTI  (lympho-epithelial Kazal-type related inhibitor) protein.

We have shown with this research that our proprietary strain of S. epidermidis can be engineered for the delivery of therapeutic proteins and can efficiently colonize both healthy and diseased skin,” said Mr. Whitfill. “Azitra is now planning further studies to evaluate the efficacy of AZT-02for the potential treatment of NS. The company is also investigating other indications—such as atopic dermatitis—for additional therapeutic uses with this platform of delivering therapeutic proteins by a commensal skin organism.”