What does Nemucore do? ▼
Nemucore is working on a drug for Acute Myeloid Leukemia (AML), a type of blood cancer. At this time, there are few options for patients with this life-limiting disease. The drug is called NMI-900. We found it to be the best-in-class drug to treat cancer, but the medical community did not have a diagnostic test to determine which patients would respond well to this drug. So, along with our collaborators, we developed a companion diagnostic that identifies which patients should be treated with NMI-900.

We have partnered with some of the top AML clinics in the world: namely the H. Lee Moffitt Cancer Center and Research Institute in Tampa, FL and the Memorial Sloan Kettering Cancer Center in New York, NY. Together, we designed a Phase 1b/2 clinical trial protocol using NMI-900 and our companion diagnostic. Now, we’re raising funds to get this combination into clinical trials to help patients with AML.

Why do only some patients respond to the cancer drug you’re developing? ▼
Historically, all cancer was treated with chemotherapy that killed cancer cells but also damaged healthy cells, which caused a lot of side effects. Science has evolved to understand that about 30% of patients with cancer have cancers with identifiable genetic mutations that can be targeted by specific drugs, called targeted therapies. We call this the lock-and-key approach: the mutations are the “lock” and the targeted therapy is the perfectly designed “key” to fit the mutant protein in the patient’s cancer. But that’s only relevant for about 30% of cancer patients – the other 70% of patients with cancer don’t have an “actionable” or “druggable” genetic mutation, therefore these very specific targeted therapies do not help them.

At Nemucore, we’re working on identifying which drug works for those 70% of patients that don’t have an identifiable genetic mutation. Right now we have a potentially game-changing solution for patients suffering from Acute Myeloid Leukemia.

What’s the new approach you’re using? ▼
To explain this, we need to introduce a couple molecules. You’ve probably heard of DNA, which is a molecule that stores genetic information in a cell’s nucleus. The second molecule is RNA, which helps code, decode, regulate, and express DNA.

Our focus is finding an effective treatment for the 70% of patients that don’t have identifiable genetic mutations in their DNA. For our lead drug, NMI-900, we’ve identified RNA signatures that indicate if a patient’s cancer is sensitive to the drug. Just by measuring a specific group of RNA molecules in the cancer cell, we can tell whether NMI-900 could help a patient by destroying his or her cancer.

What is Nemucore’s history? ▼
In 2008, the opportunity to start Nemucore arose. Even then, we understood the difference between the low-hanging fruit that the 30% of patients with identifiable genetic mutations represented and the 70% of cancer patients who didn’t have these targetable lesions. And so we took an opportunity to go after things that are common in cancer cells, and not so common in non-cancer cells, a very contrarian perspective.

We raised about $7 million through several National Cancer Institute and foundation grants, which helped us run until 2015. Our research was going well, but we couldn’t scale the company fast enough. We had an opportunity to look at a molecule that GlaxoSmithKline had created and sub-licensed to Cancer Research UK (CRUK), which is the largest cancer foundation in the world. We took a look at the molecule and found it had a lot of potential. Within four days, we had a nondisclosure agreement in place and we had access to all of the documentation on the drug.

Since then, we’ve been focused on creating the right clinical development approach to run successful clinical trials.

How has your Acute Myeloid Leukemia drug performed in trials in the past? ▼
Our drug was used to treat 36 patients in a Phase I trial conducted by Cancer Research UK. A Phase I trial is designed to test a drug’s safety and to establish the right dose. Though it’s not the primary goal of a Phase I trial, you also get some sense of whether or not the drug will work. The trial showed that the drug did have some level of clinical activity.

Tell me about the trial you are conducting now. ▼
Fast forward two years. We’re now in Phase 1b/2 because we’ve changed the dosing schedule of NMI-900 — in the CRUK study the drug was administered five days a week, consecutively, every three weeks. We’re now testing administering the drug once or twice a week, then two weeks off. This schedule really benefits patients so they’re not sitting in a hospital for five days in a row; instead they receive an hour-long infusion once or twice a week. In order to change the schedule, we have to do a Phase 1b trial.

This new Phase 1b clinical trial was designed with prominent leaders in AML, specifically the folks at Moffitt Cancer Center in Tampa, FL, and at Memorial Sloan Kettering in New York, NY. It’s for patients with Acute Myeloid Leukemia (AML), and also high-risk Myelodysplastic Syndrome (MDS), which is a potential precursor to leukemia. In this trial, we will use both the companion diagnostic and NMI-900.

At the beginning, this trial will simply collect data about the companion diagnostic: we will test each patient’s tumor a few times throughout the trial while he or she receives NMI-900 once or twice a week. This data will help us retrospectively validate that the diagnostic does in fact predict who will benefit from NMI-900. Once we have treated about 40 patients with NMI-900 and analyzed the results of the diagnostic, we can use the data and work with the FDA to open an expansion trial, in which we will use the diagnostic first, then assign patients to receive NMI-900 if the diagnostic’s results predict it could help them.

Currently, we have physicians prepared to run the trial both at Moffitt Cancer Center, Massachusetts General Hospital, and Memorial Sloan Kettering Cancer Center.

How will you make money? ▼
Today, Nemucore is poised for clinical trials of NMI-900. If these trials perform as expected, we will look to partner NMI-900 with one or multiple global biopharmaceutical companies who already sell therapies in the blood cancer market.
How can you determine how well the drug is working? ▼
Physicians will perform biopsies to look at the bone marrow throughout the course of the treatment. In Acute Myeloid Leukemia, the bone marrow that usually produces cells that carry oxygen, fight infection, and help the body form clots makes cancer cells instead. As a result, patients can’t make healthy cells. The bone marrow biopsies help analyze the extent of the cancer and the response to treatment. Because the bone marrow makes cells that circulate in the bloodstream, blood samples can also be evaluated throughout treatment to get an idea of a patient’s response.
How well does Nemucore’s AML drug appear to work? ▼
Even though initial trials are meant to test safety, investigators always look at whether or not the drug works. In this case, our team felt strongly that the drug had a really good “clinical activity signal,” which is the language that we use to talk about whether or not drugs work.

With this particular patient population, the likelihood of five-year survival is about 27%. In these particular patients, because they haven’t responded to regular chemotherapy, they may die in six to eight months. So if the drug is working, they’re going to get better right in front of the doctor’s eyes. That’s the difference with this type of disease — the patients the doctors are treating are really sick when they enroll them in the trial, and they’re going to get better even before they can prove it on a biopsy or a blood sample. Not only will they feel better but they will likely live longer with fewer or no symptoms.

The patients in the CRUK trial did well on the drug by exhibiting a “manageable” safety profile. One of them, in particular, received 11 months worth of treatment. Her cancer stabilized. Any time a patient enrolls in enroll in a Phase 1 trial, he or she has a resistant cancer, or a cancer that has been heavily pretreated that no longer responds to available treatments. Not only do these patients have aggressive cancers, but their body has really suffered the side effects of multiple chemotherapeutics because they’ve often tried everything else. When you see patients do well in that setting, it’s very encouraging

How many people could potentially use this drug? ▼
Each year, there are about 22,000 new cases of Acute Myeloid Leukemia and about 11,000 cases of death. That might not seem like a lot of patients, but the FDA isn’t interested in any more drugs that can treat all patients with cancer and see only 20% benefit; they’re interested in drugs that can treat 1,000 patients and 80% will benefit.
Where do you see Nemucore going? ▼
For us, this drug is really the tip of the iceberg. If we show that this drug can actually treat patients with AML and we can use the companion diagnostic that’s built on the principles suitable for identifying treatment for 70% of cancer patients, then we could have a watershed moment that allows us to scale our organization. We can develop a pipeline of cancer therapies using the same principles and truly help a lot of patients with cancer.
What are you currently most worried about? ▼
We’re sitting here in our office encased in data right now. We’re very convinced that the case for treating Acute Myeloid Leukemia effectively can be made. And so what keeps us up at night is whether or not we can we raise the capital to show that that’s actually the case. Everything else is sort of superfluous.
Tell me more about your partnerships with the blood cancer experts. ▼
At Memorial Sloan Kettering, we’re working with Drs. Ross Levine, Martin Tallman, and Eytan Stein. Dr. Levine runs a research lab dedicated to developing diagnostic capabilities for leukemias. Drs. Tallman and Stein are both Hematologic Oncologists, and Dr. Tallman is the Chief of the Leukemia Service. All three specialize in leukemia and blood cancers. These guys routinely publish in the New England Journal of Medicine and they see all the drugs that are going after blood leukemias. They are impressed by our ability to identify if patients will be sensitive to our drug and wanted to work with us to bring it into clinical trials.

At the Moffitt Cancer Center in Tampa, we’re working with Drs. Alan List and David Sallman. Dr. List is the President and CEO of Moffitt. His specialty is hematological oncology. Earlier in his career, he was a pioneer in the development of a drug called Revlimid. Revlimid is a wonderful drug that helps patients with Myelodysplastic Syndrome or Multiple Myeloma. It also generates close to about $8.2 billion a year in revenue, and it’s the major product for the pharmaceutical company Celgene. Dr. Sallman is Hematologic Oncologist whose research interests focus on the development of targeted therapeutics for patients with AML and MDS.

These are not just the physicians you’d find at a community health center. At the American Society Hematological Malignancies conference, these doctors would be the rock stars walking down the red carpet. We think from a clinical and scientific perspective, we’ve got a super strong story

How much financing do you need to accomplish your goals? ▼
To run this trial and do the things we need to with the regulatory agencies, we need to raise $6 million to $7 million. Over the next 24 months, we need to raise about $10 million.
Who are your competitors? ▼
Until 2017, there hadn’t been an approval of a drug to treat Acute Myeloid Leukemia for 25 years. They were using drugs that were approved in 1971. There’s no competition per se because we’re competing against the standard AML treatment, which are those drugs that were approved in 1971. When patients fail on those drugs, there aren’t really many answers. That’s when patients go into clinical trials. So, if we’re able to provide a better solution than these other drugs that were approved nearly 40 years ago, we should be able to move forward.

Just last year, there were two new drugs approved to treat AML. One of those approvals can only treat 10% of acute myeloid leukemia patients, and the other one is only good for about 20% of acute myeloid leukemia patients. In order to be a candidate to receive those two drugs, you have to have a targetable mutation. Whereas, with our drug, you don’t have to have that targetable mutation. With our companion diagnostic, we can get a pretty good indication, before administering it, whether or not it will work. So we’re fundamentally different than our competitors that were approved this year, which I think is an important differentiator.

How much will your drug cost? ▼
Historically, the price points for targeted therapies like the one we’re developing have a cost that range over several thousands of dollars. We suspect ours will probably be in this range as well, but we will not be able to confirm that until after our clinical trials are finished.

Typically what happens in the U.S. is, you get your FDA approval in a specific patient population, and you work with the Centers for Medicare and Medicaid Services to identify key aspects of the patient population that you’re going into and your expected price point.

In the UK, where there’s a single-payer system, they take into account the economics of the drug and the outcome of the drug trials. One of the great things about having had that first trial run in the UK is that we can have a more in-depth conversation about health economics with their National Institute for Council on Economics Health.

How did a small company like yours develop an innovative drug like this? ▼
The Big Pharma model has been to find a molecule and treat as many people as possible with it. What we came to understand was that that model was broken. What really needed to happen was that scientists needed to understand that each individual cancer patient had their own idiosyncratic tumor. They may respond differently to a particular medicine. Big Pharma didn’t care as long as 20% of them did well on the drug. And the FDA and regulatory agencies were approving these drugs because at the time there weren’t a lot of therapies available. There were classic radiation, surgery, and chemotherapy.

As molecular biology got more sophisticated, we could really discern which patient had what type of profile and which patients were sensitive versus resistant. Big Pharma did a great job coming up with these molecules. But to move the needle for Big Pharma, they need that drug to make $500 million six or seven years after they initially discover it, and that wasn’t the case with drugs like ours.
So smaller biotech companies like Nemucore — who don’t have to worry so much about scale at the outset and who could find the six patients for whom this particular drug will work — can create a lot of value: patients can have better quality of life and insurers no longer have to pay for what is essentially end of life care. You can improve patients’ ability to survive disease and that end-stage life care will be less expensive.

We had some underlying scientific principles. We were able to build and develop on those, and take ideas from several different organizations and bring them together. We’ve become the ultimate integrators. That integration has really taken off with our clinical advisors. Could someone come and beat us today? Probably not. Could someone come in five or ten years with differentiated therapy in that similar vein? Yeah, that’s probably going to happen. But for now, I think we’ve been the ultimate keeper of this technology and have succeeded in figuring out how to deploy it and integrate it versus being the best chemist in the lab.

What’s your timeline? When do you expect your first drug to be approved? ▼
Alnylam Pharmaceuticals has been working on RNAi technology since 2003, and just this fall, they got great headline Phase III data. It looks like that drug is going to be approved sometime in early 2018. But it cost $1.3 billion and took 15 years. For Nemucore, with the drug we have now and the companion diagnostic, we’re think we could have FDA approval in a 3-4 year timeframe. We found the drug in 2014. It’s a very short timeline.

What kinds of feedback do you get from your investors? ▼
Typically the institutional investors we talk with are either scientifically or clinically trained. What we do to de-risk the investment is talk about who we’re working with. In terms of Drs. Alan List and Ross Levine’s teams, and the clinical folks who are literally the people that are gonna put the needle in the arm of those patients of this drug — these folks see all the different drugs that are out there. For us, one of the things that we like to do for those people who don’t have a strong scientific background is to say, “Look. You can certainly believe or not believe what I’m saying, but these four people right here are going to give this drug to patients.” And I think the power of that is really palpable.
Who’s on your team? ▼
Our executive leadership team has over 100 years of biopharmaceutical experience and are truly dedicated to helping cancer patients. I love working with my team because they are innovative and know how to get drug development accomplished. This shows as we’ve been able to attract the best of the best when it comes to key opinion leaders.

Our board is made up of people with pretty incredible backgrounds. There’s Dr. Seiden, who right now is the Chief Medical Officer of the McKesson Corporation and the President of U.S. Oncology; Brian Constantino, who took the healthcare advisory practice at PricewaterhouseCoopers and built it from a $100 million business to a $1.1 billion business when he left 15 years later; Jim Farinholt, who’s started a handful of biotech companies at this point after coming from an investment banking background; Doug Bailey, who’s been an entrepreneur since he left MIT in the early 1970s and helped build Endocyte Pharmaceuticals. It’s a pretty esteemed board and they’ve bought into the story, the science, the chemistry, the clinical aspirations of what our amazing little company can do.

On the frontline of our clinical program is our director of clinical affairs, Allison Morse, who I have a tremendous amount of respect for. Allison was an Oncology Nurse Practitioner for 20 years before coming to work for Nemucore a year ago. Her passion is getting the best for patients and the ability to bring new therapies to the patients, especially those who don’t have a lot of options.

Finally, we have about 57 investors in the company who mean the world to me and our team as they have been pioneers in our effort to bring our novel approach to the clinic. When we are successful, there will be a lot of patients grateful for the risk our investors took to bring them our life-saving approach.