Primevax: Using Dengue Fever to Treat Cancer

PrimeVax is a pre-clinical biotech company who has developed a one-time one-week cancer treatment for late stage, non-responding patients using wild type dengue virus and autologous dendritic cells. They expect to enter their first clinical trial in 2017.

To learn more about this exciting angelMD company and be the first to know about investment opportunities, please follow them on angelMD.

 


The idea of harnessing the power of the immune system to battle cancerous tumors is not new. A recent BBC article, Cancer: The Mysterious Miracle Cases Inspiring Doctors, discusses one of the strategies that PrimeVax, an angelMD company, is taking.

The BBC article references a case study of William Coley, who famously observed a patient with a large tumor in his neck experience spontaneous remission after catching a nasty skin infection. He tested the principle on a small number of other patients, and found that deliberately infecting them with bacteria or other toxins destroyed otherwise inoperable tumors.

Indeed, recent evidence makes a compelling case that infection can be the key to stimulating spontaneous remission. For instance, per the BBC article,

Rashidi and Fisher’s study found that 90% of the patients recovering from leukaemia had suffered another illness such as pneumonia shortly before the cancer disappeared. Other papers have noted tumours vanishing after diphtheria, gonorrhoea, hepatitis, influenza, malaria, measles, smallpox and syphilis. What doesn’t kill you really can make you stronger in these strange circumstances.

The article goes on to point out that the microbes themselves aren’t directly responsible for the healing – the infection is thought to trigger an immune response that affects the tumor.

Further excerpts from the BBC article are below:


It’s not the microbes, per se, that bring about the healing; rather, the infection is thought to trigger an immune response that is inhospitable to the tumour. The heat of the fever, for instance, may itself render the tumour cells more vulnerable, and trigger cell suicide. Or perhaps it’s significant that when we are fighting bacteria or viruses, our blood is awash with inflammatory molecules that are a call to arms for the body’s macrophages, turning these immune cells into warriors that kill and engulf microbes – and potentially the cancer too. “I think the infection changes the innate immune cells from helping the tumours to killing them,” says Henrik Schmidt at Aarhus University Hospital in Denmark. That, in turn, may also stimulate other parts of the immune system – such as our dendritic cells and T-cells – to learn to recognise the tumorous cells, so that they can attack the cancer again should it return.

Schmidt thinks that understanding the process of spontaneous remission is vital, since it could help refine the emerging class of “immunotherapies” that hijack our natural defences to combat cancer. In one treatment, for instance, doctors inject some cancer patients with inflammatory “cytokines” in order to kick the immune system into action. The side effects – such as high fever and flu-like symptoms – are typically treated with drugs like paracetamol, to improve the patient’s comfort.

But given that the fever itself may trigger remission, Schmidt suspected that the paracetamol might sap the treatment’s potency. Sure enough, he has found that more than twice as many patients – 25% versus 10% – survive past the two-year follow-up, if they were instead left to weather the fever.

There could be many other simple but powerful steps to improve cancer treatment inspired by these insights. One man experienced spontaneous remission after a tetanus and diphtheria vaccination, for instance – perhaps because vaccines also act as a call to arms for the immune system. Along these lines, Rashidi points out that a receiving standard vaccine booster – such as the BCG jab against tuberculosis – seems to reduce the chance of melanoma relapse after chemotherapy.

Catching a Cure

Others are considering a far more radical line of attack. For instance, one approach aims to deliberately infect cancer patients with a tropical disease.

The technique, developed by American start-up PrimeVax, involves a two-pronged approach. It would begin by taking a sample of the tumour, and collecting dendritic cells from the patient’s blood. These cells help coordinate the immune system’s response to a threat, and by exposing them to the tumour in the lab, it is possible to programme them to recognise the cancerous cells. Meanwhile, the patient is given a dose of dengue fever, a disease normally carried by mosquitoes, before they are injected with the newly trained dendritic cells.
Under the supervision of doctors in a hospital, the patient would begin to develop a 40.5C fever, combined with the widespread release of inflammatory molecules – putting the rest of the immune system on red alert. Where the tumour was once able to lurk under the radar, it should now become a prime target for an intense attack from the immune cells, led by the programmed dendritic cells. “Dengue fever crashes and regroups the immune system, so that it is reset to kill tumour cells,” says Bruce Lyday at PrimeVax

Infecting vulnerable patients with a tropical illness may sound foolhardy, but dengue fever is less likely to kill the average adult than the common cold – making it the safest choice of infection. Importantly, once the fever has subsided, the programmed immune cells will remain on the lookout for the tumour, should it reappear. “Cancer is a moving target. Most therapies attack from just one side – but we’re trying to put it in a lose-lose situation, now and in the future,” says Lyday.

No one could fault the ambition behind this kind of therapy. “Our mission is to replicate spontaneous remission in as standardised way as possible,” says Lyday’s colleague Tony Chen. Even so, they are keen to emphasise that their idea is still at a very early stage of development – and they cannot know how it will play out until they begin a clinical trial. The first tests, they hope, will begin with advanced melanoma patients, perhaps by the end of the year.

Clearly, caution is necessary. As Irvine points out: “Spontaneous remission is a little clue in a big complicated jigsaw.” But if – and that is a massive if – they succeed, the implications would be staggering. A rapid, relatively painless recovery from cancer is now considered a miracle. The dream is that it might just become the norm.”

» Read the full article on the BBC’s website here.


With the advent of immune-oncologic agents, we are entering a brave, new era of cancer therapeutics. Several companies already have seen early clinical and commercial success with treatments that target a facet of the immune-modulated innate response to tumors. Thus, there is no doubt that the future of anti-cancer therapy lies in harnessing the power of the immune system. PrimeVax is poised to enter this exciting market with a unique approach that is poised to play an important role in treating cancer.

If you’d like to know more about this exciting angelMD company, please follow PrimeVax on angelMD to be included in exclusive communications about progress and investment opportunities.

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New Years Recap

new-yearAs 2016 comes to a close, we want to celebrate the amazing year we’ve had at angelMD.  We’ve seen tremendous growth in our physician and startup networks, exceeding our expectations on both fronts. We are grateful for the time you, our physician members, have spent reviewing startups and considering joining angelMD syndicates.  As a result, many startups and every syndicate received extensive diligence and feedback from medical professionals which helped fellow investors make better investment choices.  In 2016, we successfully completed 10 syndicates, providing much needed capital to those startups.  angelMD physician members have provided significant support and networking to many of our startups, giving them feedback, guidance and helpful introductions.

2017 is already shaping up to be a fantastic year for angelMD. You’ll soon see a newer, more sophisticated website to help you follow companies, track your investments and learn.  We will introduce sophisticated data tools to help analyze startups.  With tools like this, we can give startups actionable information to maximize their chances for success as well as deepen our investors’ understanding of companies prior to making investments.  Q1 will also see the first angelMD fund designed to accelerate and support syndicate investments and provide members a vehicle to efficiently spread their capital across a portfolio of companies.

As we say goodbye to 2016 and welcome 2017, we’d like to take a moment to give thanks to all of the physicians that have spent their time with us online and at our events.  The life-blood of angelMD is your participation.  We know that your time is precious and we are working to provide you with an experience that is both valuable and efficient. Together we will continue to transform the world of healthcare investing and support innovations that will change the world.

Have a happy and healthy new year!

Warm Regards,

Orrin Ailloni-Charas, MD &

The angelMD Team

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Curtana – New Syndicate

curtanaangelMD is pleased to announce the formation of its newest syndicate for Curtana Pharmaceuticals. Curtana has developed a first-in-class molecule, CT-179, for the treatment of glioblastoma.  GBM is an aggressive brain tumor seen in both children and adults and carries a very high mortality rate, even with current best available therapy. angelMD had a chance to talk to Curtana CEO, Dr. Greg Stein and learn more about their important work.

Please send an email (startups @ angelmd.co ) to be included in exclusive communications regarding the angelMD syndicate for Curtana or register for one of the scheduled webinars with CEO Greg Stein, MD, MBA HERE.

  1. What drew you to the field of glioblastoma?
    It was a combination of three things. First, I really liked the science story.  I have looked at hundreds of opportunities over the years and this one was very compelling in terms of what could potentially be done to treat brain cancer.  Second, I was thoroughly impressed by the inventor, Santosh Kesari, MD, PhD, who, at the time, was the head of Neuro-Oncology at the UC San Diego Moore’s Cancer Center.  He is one of the top brain cancer researchers in the country and someone who is passionately committed to improving the lives of his patients.  Lastly, I had recently lost a friend to GBM.  Even though I am a physician and have seen many people die, it was a much different experience to watch someone for whom you care be devastated and die from this horrible disease.
  1. For those less familiar with glioblastoma, give an overview in a few sentences.
    Gliolastoma, or GBM, is the most deadly and most common of the primary brain tumors in adults with close to 11,000 new cases diagnosed in the U.S. each year. The tumor is very aggressive and, even with the best available care, which often includes surgery, radiation therapy, and chemotherapy with temozolamide, the median survival time is only about 15 months.
  1. How is CT-179, Curtana’s signature molecule, different than other proposed therapies for GBM?
    CT-179 is unique in that it directly targets the glioma cancer stem-like cells (CSCs), which have been shown to be responsible for tumor initiation, by blocking a transcription factor, Olig2, that is, for the most part, only active in the cancer cells. In addition, Olig2 has been shown to be a key driver of resistance to radiation therapy and migration of the cancer cells into normal brain tissue.  Lastly, because Olig2 is just found in the cancer cells, the compound will be much safer and better tolerated than traditional chemotherapeutic agents.
  1. What third-party validation have you received from the scientific community?
    Many researchers are aware of the critical role that Olig2 plays in glioblastoma and other gliomas, which has allowed us to establish research collaborations with some of the top brain cancer researchers from such institutions as MD Anderson Cancer Center, Baylor College of Medicine, Mayo Clinic, John Wayne Cancer Institute, Children’s National, and the Hudson Institute in Australia. Preliminary results from these efforts have been encouraging and everyone wants to keep working with us so we can better understand how to best use CT-179 to help patients.
    Curtana has also been the recipient of two scientific grants. The first was an STTR grant for $225,000 from the National Cancer Institute at the NIH. In today’s environment, only about 5% of applications to the program to which we applied receive funding. The second one was a $7.6 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT). That grant application process was very competitive and quite rigorous. It required passing a thorough evaluation by an independent 15-member product review committee that was comprised of experienced pharmaceutical and oncology experts from around the country.
  1. What interest in Curtana have you had from industry?
    We have been talking with many of the big pharma companies since the time the company was started back in 2013. Several companies have been impressed by the progress we have been making and, once we reach the clinic, have expressed an interest in potentially working with us. Although I can’t be specific, one of the top oncology-focused big pharma companies recently indicated that they would like to explore a potential research collaboration with Curtana starting next summer. There is also a Japanese pharma company which has indicated they would like to purchase an option to license Curtana’s technology for Japan and other countries in Asia. If we are able to close this deal sometime early next year, it should provide us with most of the working capital we will need to advance CT-179 through early clinical development.
  1. How do you think syndicating an investment with angelMD will benefit Curtana?
    It will be tremendously validating as angelMD is comprised of physicians who understand the science and the promise of what we are doing. This validation will be important to other potential investors, who often find the science story to be too hard to understand. Moving forward, the relationship with angelMD and its large network of physicians should allow us to identify potential collaborators as well as promote the story to the medical community.
  1. Tell us about your team and their unique capability in this specific field?
    As I mentioned previously, my scientific co-founder, Dr. Kesari, is one of the top brain cancer researchers in the country. He heads our scientific advisory board and has given us access to just about anyone in the field with whom we want to talk or work. My two senior scientists, Drs. Graham Beaton and Gordon Alton, each have over 20 years of experience in the pharmaceutical industry either working on or leading numerous preclinical drug development teams at big pharma companies and start-ups alike. Their experience and expertise is evident in the phenomenal job they have done over the past couple of years to the point where we now have a great looking molecule, CT-179, that we plan to advance into human clinical trials.
  1. What advice do you have for new biopharma entrepreneurs?
    First and foremost, be prepared for what you are getting yourself into. The task of developing a new drug takes many years and a lot of hard work with numerous ups and downs along the way. Second, surround yourself with the best people you can find. Drug development is a team sport, so you want to be sure that you have a team that knows what it takes to win!
  1. What mistakes have you made in the past that have made you a better entrepreneur?
    This question could probably be a blog post by itself! One of the biggest mistakes I have made in the past is not being more selective about the people with whom I work. Someone may have a superb looking resumé, but that often doesn’t tell you what that person is like to work with and what their core values are. I am now much more careful about screening the people with whom I may work and making sure that they are not only very smart, but they are someone who is highly respected and is seen as someone who is an excellent team player.
  1. If you had to single out one of your key company goals for the next 12 months what would it be?
    Our singular focus at Curtana is to complete all the activities needed to file an IND application with the FDA for CT-179 for the treatment of glioblastoma by the end of next year.

 

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Eko Devices – a Physician’s Perspective

ekobOne of the exciting things about being a physician in the angelMD network is the opportunity to see innovations that will influence healthcare in the years to come. Sometimes we get to meet and mentor companies that have the potential to transform the practice of medicine today. Eko Devices is a company that can do both.

The launch point for Eko is the Eko Core stethoscope, which currently is on the market. As a practicing anesthesiologist, I have found its clarity and amplification to be an enormous advantage in the noisy operating room.

On a recent OB shift, I had the opportunity to demonstrate the Eko Core to our neonatal resuscitation team. The ability to discern heart sounds and bilateral breath sounds is essential during a neonatal evaluation and resuscitation. In fact, new Neonatal Resuscitation Protocol guidelines for 2017 state that initial heart rate assessment in a newborn should be performed by auscultation, rather than the more traditional, but unreliable, umbilical cord palpation.

Using the Eko Core stethoscope on a newborn, with up to 40x amplification, was a “Wow” moment for the team. All patient resuscitations are a time-sensitive team effort, all the more so when the patient is a newborn.  Hearing a newborn’s heart and lung sounds clearly with the Eko Core, an often difficult task with a traditional stethoscope, is more easily accomplished. Seeing a newborn’s phonogram in real time lets the entire team see the heart rate, allowing for smarter and faster team decision making.  As a result, newborns get precision care in their first moments of life.

Eko Devices has the power to transform the way medicine is practiced, by allowing doctors and nurses to do the jobs they already understand, but better. All time-sensitive cardio-pulmonary decision making can be enhanced through the use of the Eko Core.

angelMD is pleased to enable its members to participate in an investment syndicate that will close out the currently oversubscribed Eko investment round. Members may request information by email at: startups@angelmd.co.

Orrin Ailloni-Charas, MD, MBA is a practicing anesthesiologist in the Bay Area and an angelMD Regional Medical Director.

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Venture Capital and Risk

Changing the risk profile of early stage investing

Orrin Ailloni-Charas, MD, MBA


Venture investing is fun and exciting. You get to meet passionate innovators who want to change the world and experienced advisors who already have. When your time and money are invested well, you get to watch and participate as entrepreneurs go on the adventure of a lifetime and produce healthy financial returns in the process.

Unfortunately, more often than not, money invested in early stage companies is deployed without any return on investment. In fact, the majority of investments end as complete losses or with only modest gains. The actual statistic is that about 1 in 20 companies will succeed. While this is the norm, the reality is that the industry is unnecessarily amateurish and risk can be more effectively

Most venture capitalists and angel investors understand that only a small percentage of their holdings will produce significant returns. Thanks to those successes, the internal rate of return (IRR) for a well managed portfolio is high. (According to recent studies the average IRR for a portfolio consisting of at least 10 investments is 26%.)

The goal of angelMD is to mitigate risk and transform early stage investing into a sophisticated data-driven investment class. This is accomplished with three primary tools…the combination of which is unparalleled.

 

Pipeline: With the largest network of medical startups in the world, angelMD is able to source and evaluate potential deals with an incredible array of data and is able to compare and contrast companies across a given sector.

 

Experts: An extensive physician network shows interest through polls, surveys and proactive support. Members also participate in events, such as a regional Medical Innovation Clubs, Pitch Events and angelMD hosted webinars throughout the month. The feedback from the extensive physician network is a critical and unique component of the angelMD evaluation model.

Next, as startups work their way through the angelMD evaluation process, they eventually get reviewed by the angelMD Scientific Advisory Board (SAB).

As the top tier of startups is identified, the company invests additional effort to form an investment syndicate or refer the company to the angelMD Catalyst Fund.

AngelMD is also adamant that an investment model reliant on “picking winners and losers” is antiquated and limited. Instead, we believe in “making” winners by going to work post investment to drive better outcomes. We are able to leverage our network of  physicians, hospital and industry executives and others to support and accelerate portfolio companies…investing as much or more effort post investment than pre investment.

 

Software: As the CTO of angelMD likes to say, “We are a computer science experiment.” Investment activity conducted on the platform leverages internal metrics and a proprietary scoring system to compliment and leverage the “power of the crowd." The angelMD scoring system is a sophisticated algorithm that analyzes metrics important for a successful start-up and enables angelMD to track the progress of each company against their score. A team’s ability to meet milestones, both self-imposed and at the suggestion of angelMD, is constantly being monitored and measured.

Investing successfully requires an edge. angelMD does not rely on a silver bullet or make lofty promises. Instead its developing a sophisticated system that connects startups, physicians, investors and industry at scale only possibly in a digital model. At every turn, risk is being evaluated and mitigated to drive better outcomes.

 

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