I had a great meeting with our client Masashi san, who is an intrepreneur from Panasonic R&D company of America in Silicon Valley. #StartupFire partner Stoooc has been working with him for developing C2C platform that allows mature adults to mentor younger adults who are seeking advices and perspectives on their life decision.
I attended the Deep Learning & AI Assistant Summit organized by ReWork in San Francisco. The speakers in the conference were top AI experts from companies like Google, Facebook, Amazon, Uber etc.
There were also presentations by startups and a demo stage where some of the selected startups showed their work. Deep Learning is a hot and rapidly evolving area. It is a powerful subfield of machine learning, based on algorithms inspired by the brain called artificial neural networks.
The algorithms automate the extraction of representations from data, and have helped solve challenges in: computer vision, natural language processing, speech recognition, video processing and image recognition.
Personally I found a presentation by Disney Research’ Michael Carr very interesting. It was about modelling team strategies using Deep Imitation Learning. They had developed an automatic “ghosting” system for a basketball match which illustrated where defensive players should have been (instead of where they actually were) based on the locations of the opposition players and ball.
An AI assistant is a software agent that can perform tasks or services for an individual. An automatic chatbot, Apple’s Siri and Amazon’s Alexa are examples of AI assistants. Natural Language Understanding is the next big challenge to conquer to create great AI assistants. This will enable companies to build realistic conversational interfaces and smooth dialog between AI and user. There were some interesting applications for AI assistants presented in the conference. For example a company called Woebot was developed to address the growing crisis of mental health. Woebot is an automated conversational agent (chatbot) who helps you monitor mood and learn about yourself by chatting with an AI.
This was an excellent conference for networking and getting to know the current state of Deep Learning and Assistant AIs.
I had a meeting with Dr. Sean Huver, CEO of Deep Science, a top startup in the recent Alchemist Accelerator class. Deep Science is revolutionizing the use of AI in the security industry by performing realtime threat detection. Their AI has been trained to spot robberies as they’re occurring and to get help immediately. They have 4 upcoming pilot projects with top 100 retailers.
Join 7,000 founders in Silicon Valley for 2-days of nonstop content – fireside chats, Investor Q+A’s, hands-on workshops, educational sessions; plus invaluable networking opportunities with your fellow attendees, 300 exhibiting startups, and our great partners. Don’t miss out. We hope to see you this year for our 6th annual event.
Reid Hoffman – Co-founder of LinkedIn | Partner of Greylock Partners
Jeff Jordan – General Partner of Andreessen Horowitz
Dr. Andrew Ng – Coursera, deeplearning.ai, Stanford
Max Levchin – Co-founder of PayPal | CEO of Affirm
Guy Kawasaki – Evangelist of Canva
Walt Mossberg – Top Tech Influencer | Co-founder of Recode
Adi Tatarko – Co-founder & CEO of Houzz
Kyle Vogt – Co-founder & CEO of Cruise Automation
James Park – Co-founder & CEO of Fitbit
Baron Davis – NBA All-Star
Baiju Bhatt – Co-founder of Robinhood
Vinny Lingham – Co-founder & CEO of Civic Technologies (Bitcoin)
Dan Pink – Bestselling Author – Drive
Mary Grove – Director of Google for Entrepreneurs
and many more…
We really appreciate to 42 Family. They give us the great space for holding #StartupFire, and also provide foods & drinks……As i always like to organize the event, and not easy to find the great venue……They are so kind to prepare for the everything our guests need and enjoy the event. We both believe Education is the key to save the world, and Love is the answer❤️
Always great to visit in 42, amazing place, design, and people!!!! so friendly and respectable
Capacity: 200 Participants
100 guests from Facebook & Eventbrite
100 students from 42
* There is a large parking area at 42.
I bought 42 hoddie, and took a group photo with 42 family.
Our HIPHOP Group ‘KAZOKU’ means Family in Japanese too.
Dj Domo will join #Startup Fire to welcome all guests by playing great music♪
We enjoy talking about ‘Free Movement’ by #StartupFire.
We made sandwich Looks like we can sell this haha
So, we discussed about our next #StartupFire, and our CTO Andrew will talk about ‘3 lessons from working for Facebook & Google’, so it will be a great opportunity for participants to learn how to be a great engineer and also leading your team.
Come Dream With us, Lets Save the World, Love is the Answer❤️
Ms. Jeanette Mucha CEO, Chief Science Officer and Co-Founder of SciBac.
‘SciBac designs live biotherapeutics to treat and prevent antibiotic resistant disease in the microbiome’
1. What’s your name, and please tell about your background.
My name is Jeanette Mucha, I am CEO of SciBac. I don’t have the typical background of a scientific founder. After graduating with a bachelor’s degree in Biology at the University of Miami, I taught high school biology and marine biology in Miami and Ft. Lauderdale. This was an important experience for me, because it taught me how to learn. In school, I had been good at memorizing and regurgitating information, but I did not retain much past the test date. When I had to figure out how to explain concepts like evolution to students who were hearing of it for the first time, it is then that I developed a deep understanding and appreciation of biology. It is teaching that let me see errors in text books and assumptions that needed to be challenged. It piqued my curiosity for research in a way that may not have happened had I taken a traditional path straight into a PhD. I switched careers to research and development taking a position at Genencor (now DuPont) back when they had an immunology division. Here I became well versed in human immunology, specifically in the humoral and effector immune response. I started out testing engineered enzymes for allergic reactions, and finished my time there by co-inventing a method to identify and create kill T cell epitopes, which can be used in cancer T cell therapeutics.
I then took a few years off with two young kids which led to my participation in long distance triathlon. During that time, I excelled at the 140.6 mile Ironman distance division (a consecutive 2.4 mi swim, 112 mi bike, and 26.2 mi run) where I qualified for and competed in the 2009 World Championship. Since then, I have completed all 18 Ironman distance races that I have started. Ironman is similar to my current start-up technology. When you first hear about it, at first you think, “that can’t be possible,” but if you put in the necessary preparation and you are persistent, the impossible is possible. Also in 2009, I resumed my research career at Cobalt Biofuels where I became an expert in microbiology, strain improvement, and fermentation. Here, I earned a scientist level position and was the lead inventor on 90% of the microbiology IP. When Cobalt folded in April of 2015 due to the drop in oil prices, the strain improvement IP and strains were mentioned in Biofuels Digest as Cobalt’s “most valuable technology.” The end of Cobalt was the beginning of my start-up, SciBac.
2. Please explain your startup how did you get started?
SciBac designs live biotherapeutics to treat and prevent antibiotic resistant disease in the microbiome. Our founders, including myself, Anthony Cann, and Derik Twomey are all strain improvement and fermentation experts. We noticed that even though probiotics have historically not done convincingly well in scientific papers to display efficacy, no company that we were aware of, was attempting to do strain improvement on probiotics to give them efficacy. I had an idea for our DRIVE technology (Directed Recombinant In Vitro Evolution) where we could use directed evolution and phenotypic screens to induce gene transfer across different species of microbes. We could use this technology to move therapeutic and survivability traits into scalable probiotic species. When the doors closed at Cobalt, myself and three former co-workers decided to form a start-up that was not commodity based while helping to solve a serious threat. The four original founders pooled money to buy lab equipment and I built a lab in my garage to prove out my idea for our DRIVE technology. Yes, we literally started the company out of my silicon valley garage. Using different species of commensal and probiotic strains I was able to induce gene transfer using chromosomal antibiotic resistance as a marker. It worked and SciBac was formed. With support following a friends and family round, we moved into Molecular Sciences Institute, in Milpitas, so we could work on improving probiotics to use as therapeutics.
As we were anaerobic fermentation experts at Cobalt, we knew which organisms could easily take down a Clostridium culture. We started there and used mechanism of action when choosing the bugs to work with. In addition, Clostridium difficle infection (C diff), a type of deadly diarrhea, had already affected two founders. My husband’s grandmother had died several years prior following complications from hip surgery and a C diff infection. Derik Twomey had recently spent several months helping nurse his father back to health after several recurrences of C diff following heart surgery. As we sought to develop our therapeutic, we discovered that because of the reliance on other microbial neighbors in the gut, the lack of available nutrition and reduction of diversity was not providing enough nutrients and led to the death of beneficial wild-type organisms in the gut. C diff only starts to make toxins in the colon when protein sources are low. The toxins break open colon cells to provide nutrients. Beneficial bacteria don’t have the pathogenic ability to reap nutrients from human cells and so many die in these suboptimal gut conditions. Many wild-type probiotics thrive in optimal, healthy conditions, but lack the traits to survive a sick gut. We have set out to improve probiotics to be effective therapeutics. In other words, we set out to make better bugs as drugs.
3. Whats your role in your startup now?
I started off as the Chief Science Officer and after a year and half became CEO. As CEO, my main role is to raise money. Last April, we gained investment from the Thiel Foundation’s Breakout Labs ($350,000 convertible grant) – they have been fantastic and continue to support us. We have expected revenue in 2018 of $500,000 based on executed pilot project contracts with two industrial companies including Novozymes and a another company on the fortune 500 list. These projects are for proof of concept of our DRIVE technology so that we can then license our technology for uses outside of human therapeutics. I’m currently raising a $500,000- $1,000,000 seed to secure a non-dilutive $2.5-3MM grant which will support pre-clincals and Phase 1 for DiffiKil.
As a CSO at heart, I also have a major hand in crafting our pipeline. Our vision is that in 10 years we will have shifted the paradigm of how antibiotic resistant disease is treated in the gut and lungs, saving tens of thousands of lives from C diff and increasing the quality and longevity of cystic fibrosis patients’ lives. Our overall mission is to use DRIVE to designefficacious, safe microbes to tackle the world’s modern-day plagues.
4. Who are your customers, and what problem are you solving for them?
Our customers are patients without solutions to their infections. Our core business is focused on developing therapeutics for tackling antimicrobial resistance in the microbiome. Antimicrobial resistance (AMR) is on pace to surpass cancer deaths by the year 2050 and represents a $40B unmet need.
Our first indication is a three-hybrid strain live biotherapeutic that treats and prevents Clostridium difficile (C diff), a type of deadly diarrhea often contracted in hospitals following antibiotic treatment. $5 Billion is spent each year to treat C diff infections in the US and current solutions only provide incremental changes in recurrence rates. DiffiKil addresses all aspects of the disease by killing the C diff directly, preventing C diff binding, neutralizing toxins, and stopping spore formation. We will at first seek for FDA Biological License Application (BLA) approval first for the recurrence of the disease. However, we envision DiffiKil eventually being used as a preventative; given to anyone over age 65 entering the hospital for treatment involving antibiotics.
Our second indication, Aeruguard, is in development is for chronic Psuedomonas, Staphylococcus and Mycobacterium infections in cystic fibrosis patients, a $3.5B market with other applications in respirator infections ($400M) and chronic wounds ($18B). In all markets, antibiotic treatments fail as these microbes hide and become metabolically inactive in biofilm. Our single, inhaled or topically applied therapeutic, Aeruguard, is a motile hybrid that can dissolve biofilm, kill inactive versions of these pathogens where they hide, and reduce the viscosity of the mucus to help patients physically clear the infection. One of the extra cool things about about Aeruguard is that it is a motile, inhaled therapeutic. Most lung therapeutics have a delivery problem; can you get your small molecule the right size to enter the infected part of the lung? Aeruguard, on the other hand, solves this problem by being able to swim to the site of infection.
5. What is unique about your solution? What is your unique insight?
The microbiome is hot right now. Using live microbes to treat infections locally in the microbiome reduces toxicity and side effects commonly found with small molecules. The problem is, many wild-type microbes with therapeutic properties cannot survive inside a human, or the ones that can falter when illness strikes, or the pathogen adapts. With our DRIVE technology, SciBac can move therapeutic traits from untapped soil microbes into probiotic bacteria capable of surviving inside a person. In addition, by directed evolution, we can give these probiotic bacteria tools to survive a diseased environment, including fever resistance and the ability to make essential amino acids. Furthermore, we can increase the variety of carbohydrates that can be used for consumption including starch, a sugar source more commonly found in the gut. Like breeding a mule, where one combines the strength and patience of a donkey with the athleticism and speed of a horse, our hybrids retain the best traits from both parents. Our method patent for DRIVE is wholly owned and issued in the United States (we are expanding to Europe, Asia, and Australia in May), so no other company has the freedom to operate using our technology. We are also able to patent all our strains and indications. Since our technology has many other industrial applications, we can out-license to industrial companies following successful initial pilot strain improvement projects. This will provide nondilutive funding as well as the possibility of multiple exits.
6. How does your product actually work?
Our C diff indication, DiffiKil, is a 3 hybrid strain cocktail made up of two lactobacillus hybrids and one yeast hybrid. The three strains are lyophilized and taken orally in capsules designed to dissolve in the colon. Unlike current solutions and others in development, DiffiKil has four mechanisms of action. Most solutions, only have one or two mechanisms and, therefore, are more easily overcome by the pathogen. In our DiffiKil cocktail, there are two lactobacillus hybrids which make bacteriocins; these are small peptides that poke holes in C diff cell walls. These bacteriocins, like antibiotics, kill the C diff directly. This is where antibiotics stop – direct killing represents a single mechanism of action and just takes a single point mutation for pathogens to overcome. If you haven’t seen Harvard’s antibiotic evolution experiment visualizing this, check it out here. One of the other ways C diff can evade antibiotics is by forming spores, an inert version of themselves which is very hard to kill.
DiffiKil’s second mechanism is also produced by our lactobacillus hybrids as they prevent the binding of C diff to the colon. We are unaware of any formulation in development that shares this mechanism of DiffiKil.
Our third mechanism comes from our hybrid yeast. Our yeast hybrid has been improved to increase C diff Toxin A and B neutralization and can inactivate 96% of the toxins produced by a pure culture of C diff in just over two hours. Toxin B destroys colon cells and can cause translocation and sepsis in affected patients. This is similar to the single mechanism found in Merck’s monoclonal antibody, Zinplava. However, Zinplava has no other activity and therefore relies on antibiotics and the patient’s own immune system to clear the actual C diff bug.
Our fourth mechanism prevents the formation and germination of C diff spores. We are working to understand exactly why this is, but unlike antibiotics which can cause spore formation, our co-cultures on both solid and liquid colonic medium stop C diff spore formation. Even though we start the culture of C diff using spores, none remain or are formed when we add our DiffiKil bugs. Finally, to improve growth and survival in a C diff disease state, our lactobacillus and yeast hybrids have a wider range of carbohydrates that they can consume including starch and raffinose. They can also make all of their own essential amino acids and can survive high fevers often present during the infection.
7. How big is your market?
Our overall target AMR market is at $40 Billion and growing. The C diff market represents $5B of that $40B market. Our second indication, Aeruguard, which would be used to treat and prevent chronic infections in cystic fibrosis patients, represents a $3.5B market. Our DRIVE technology has the advantage of allowing us to quickly design cures for infections located in the microbiome and so the possibilities in our pipeline are extensive. In addition, since DRIVE is considered “natural” or non-GMO in the states, there is extensive interest in our technology in the areas of animal health, agriculture, enzyme production, and manufacturing. Our industrial projects will bring in licensing revenue as well as the possibility of multiple exits.
8. What is your business model?
SciBac is a longer term investment; you will have to be patient as we navigate the FDA approval pathway! Therefore, drug revenues are seven years out. In the meantime, we have our industrial strain improvement projects to bring in revenue, and we are currently negotiating a $2.5-3 million dollar non-dilutive grant to help push our lead indication, DiffiKil, through Phase 1 in Australia and IND approval in the US.
9. What is your go-to-market strategy?
We believe our four mechanisms of action in DiffiKil will represent a step change in patient outcomes that closely mirrors the success of fecal microbiota transplant (FMT). Current solutions are only offering incremental changes in patient outcomes for recurrence. Since payers have moved to value based pricing, it’s necessary to provide a step change in outcomes over the standard of care. Since we have four mechanisms instead of a single (or unknown) mechanism in competing products, approval and adoption are achievable. Our goal is to show human efficacy in clinical phase 2 or 3 and either partner for the indication or sell. We do not wish to compete with established pharma marketing and distribution teams, so our strategy is an exit via a buyout or partnership following successful trials.
10. Who are your competitors and how are you different?
Let me reiterate that we have four mechanisms of action and unlike other microbiome approaches, we have improved our bugs’ survival in disease conditions. No other standard of care or consortium in development has all of these mechanisms, nor even three of them. The difficult to manufacture, wild-type, beneficial microbes that like Seres and Vedanta are using in their consortiums have not evolved to survive the low nutrient conditions found in a C diff disease state by themselves. That means natural consortiums that are going into trial must have the entire microbial community present that is involved in providing those nutrients, otherwise their strains will not grow nor be active.
Multiple mechanisms not only increase efficacy, but they also make it more difficult for the pathogen to become resistant. C diff will have to evolve to combat all four of DiffiKil’s mechanisms whereas antibiotics have only a single mechanism of killing that is easy for the pathogen to gain resistance. Merck’s Zinplava must be used in combination with antibiotics, and only offers an incremental improvement in recurrence rates with its single mechanism of action. Rebiotix, who recently finished a Phase 2 study to provide a safer version of FMT, does not match FMT efficacy and requires an enema. It also has the issue of requiring human donors which is expensive, inconsistent, and costly. In addition, their treatment group results are curiously reported in comparison to historical controls instead of their own study’s controls. This suggests their own controls had low rates of recurrence. Seres Therapeutics recent disappointing clinical results likely stems around the inconsistency of human donors, a lack of known mechanisms, as well as their decision to optimize gut therapeutics in a mouse model. Even if you have even just a rudimentary understanding of the pH scale and biology, you can understand why live biotherapeutics in the pH 4.0 gut environment of a mouse will have a completely different metabolism in the pH 7.0 environment of a human colon.
The entire microbiome sector needs a better translational animal model. Due to the lack of a translational model, our current strategy is to do our Phase 1a and 1b in Australia so that we can get into humans as fast as possible. If we should find efficacy or safety is not a clear step change from the standard of care during a Phase 1b, we have the advantage of being able to use our technology to go back and improve our therapeutic strains to increase expression of a factor or move therapeutic properties into a different species.
11. What is your vision, your true North?
C diff is an infection mainly of the aged resulting from dysbiosis, an imbalance of microbes in the gut flora, that occurs following antibiotic treatment for a primary infection. What if antibiotic use is a less obvious trigger for many of our other modern-day plagues like Alzheimer’s, Parkinson’s disease, and autoimmune disease which have increased in frequency since the commercialization of penicillin? Most broad-spectrum antibiotics are indiscriminate bombs; they are not specific for the species causing the infection and, thus, have the unfortunate side effect of also decimating the beneficial bacteria which are an integral part of your microbiota. In a healthy gut, beneficial bacteria help to digest your food, prime your immune system, and outcompete opportunistic pathogens to stop harmful strains from growing.
Since the amazing advent of antibiotics in the 1940s, these modern diseases have emerged and many have recently been correlated with specific populations of bacteria. The manifestation of these diseases is certainly more complicated than any obvious bacterial infections such as C diff; they likely involve genetic predispositions and metabolic interactions with our microbiome that medical science is just beginning to decipher. Without any hyperbole, we are standing on the precipice of a new paradigm of medical thought. A recent peer reviewed paper has shown that fecal matter taken from a mouse with Parkinson’s and transplanted into a healthy mouse gives that recipient mouse the disease. As the scientific community unravels these mysteries, SciBac’s technology will be ready – allowing us to fortify the microbiome against many of these diseases.