Founder Profile: The Future of AML Cancer Treatment With Co-Founder & CEO of Nemucore Medical Innovations

Back in 1992 I met Sam Wohlstadter, one of the founding VCs of Amgen, while working for a landscape design expert. I was getting my Bachelors in Biochemistry at the time, and we hit it off. His stories of founding Amgen were quite inspirational and he advised me to get my PhD and then think about getting an MBA.

After I finished my PhD in molecular biophysics at the Medical College of Virginia in Richmond, some professors and I started a company called BioCache Pharmaceuticals. We were developing cancer vaccines for patients with adenocarcinoma which can be found in a number of different tissues in the body. We wanted to create semi-patient specific vaccines that were easy to manufacture and readily presented adenocarcinoma epitopes to immune cells called antigen presenting cells to stimulate a robust T-cell and antibody response against a patient’s tumor. It was especially important for this vaccine platform to have scalable manufacturing at a reasonable cost which we achieved.  

We were about to finish a $5MM Series A in 2001, but the capital market for early stage biotech companies froze that fall. We employed 12 people at the time, so I had to cut it down to 2 paid researchers and myself. I went to Boston University to get my MBA but continued to run the company as the uncompensated executive.

We made significant progress and were working with our collaborators at Memorial Sloan Kettering Cancer Center to design and run a clinical trial in patients with relapse/refractory adenocarcinoma. Unfortunately in 2004, the government decided that the grant program that would fund the trial was being eliminated.

I was certainly in a corner at the time, but it turned out that PwC was looking to build their precision medicine practice because business models in this space were so nascent.  We worked with clients to hone down what it meant for payers, providers and biopharmaceutical companies to examine how precision medicine strategies could be commercially implemented. I enjoyed my time at PwC and some of my work was recognized with the Chairman’s award but I always knew a time would come when I could go back to creating innovative biopharmaceuticals.

In 2008, the opportunity to start Nemucore arose and we focused on multidrug resistant cancers because in the end these are the types of malignancies that kill patients.  We needed to ameliorate the factors that promote drug resistance in order to improve patient survival.

As an example, if you’re depending on a drug to pass in to a tumor, sometimes there isn’t enough blood flow through the tissues for treatment to work.  We had to figure out how to circumvent biological barriers at the anatomical and cellular level to improve treatment sensitivity.

Michael Seiden, the chief medical officer of McKesson and current head of US oncology, is on our board and saw the writing on the wall that our pipeline could take several years of further development to get into the clinic.  However one of our assets was clinic ready so the decision was made to focus all our attention on clinically developing NMI-900.

Through a innovative partnership, we developed a companion diagnostic that allows us to determine if a patient’s tumor is sensitive or resistant to NMI-900. It measures RNA signals of sensitivity and resistance in a patient’s particular cancer.

Most diagnostics measure a protein on a cancer cell or a mutation in the DNA. We knew from our multidrug resistance studies that the cancer cell’s RNA is an important indicator of whether or not it is sensitive to a particular cancer drug. Our companion diagnostic looks for the presence of RNAs from genes that drive resistance and sensitivity to NMI-900. Then a software algorithm calculates the results in to a standard score from 0 to 100 that a clinician can use to determine the patient’s sensitivity to NMI-900. Once we had this digitized RNA signature we used publicly available transcriptome data to examine at over 5000 patient’s cancers. What we found is that AML and other blood cancers have the highest sensitivity to NMI-900.

Those with solid tumors can be treated with NMI-900 but need a combination therapy to potentiate complete tumor eradication, so we have a plan to work with Mass General to develop the right combination therapies for lung, breast, and ovarian malignancies. Right now we are preparing to run a phase 1b/2 clinical trial at Memorial Sloan Kettering and Moffitt Cancer Centers in AML.  This trial will produce the data to validate the diagnostic and level of NMI-900 a patient should receive to see a clinically relevant response.

Hypomethylating agents were approved in ~1973 for AML and it was not until 2017 that another drug was approved to treat AML.  Those drugs usually have an initial overall response rate between 60% and 80% but the response is not durable and most patients relapse with most becoming refractory to the standard of care therapy.

In our view,  to improve outcomes in AML patients we have to identify the most sensitive patients to a particular therapy and in most cases only select the upper two-thirds of patients who will achieve a clinical response.  In precision medicine it is unfortunate that we won’t be able to treat some patients, but we are sparring them the toxic side effects and doing a lot of good for the those patients who will get therapeutic benefit.

A phase 1 trial in heavily treated  solid tumors was performed before the diagnostic was developed. Once we used the diagnostic to examine the transcriptome data from 5000 patient’s cancers, we realized NMI-900 should have been developed as a monotherapy blood cancers. Although there were some significant responses in solid tumors like ovarian cancer, we had to pivot the development strategy to focus on blood cancers.

For approval we will have to run a pivotal trial that proves the prognostic value of the companion diagnostic and show NMI-900 is effective in the patient population that is selected with the companion diagnostic.  Today, we feel AML gives us the best indication to use NMI-900 as a monotherapy to help patients and achieve data suitable for regulatory approval.

That’s difficult to answer because it depends on the situation. You might be able to get a particular patients leukemia free, but sometimes because of their age they won’t elect for a long-term solution like a bone marrow or stem cell transplant. Our measure right now is to achieve responses in patients that trained pathologists agree represent clinically relevant decreases in disease burden.

The biopharmaceutical industry is trying to educate the payers about the economics behind the process. I would say right now over 70% of the oncology drugs approved today have companion diagnostics associated with them.

Recently we have seen cases where a biotech companies use companion diagnostics that show there addressable market less than 10K patients annually in hard-to-treat relapsed and refractory cancers, but they command substantial billion dollar market caps.  The underlying assumption supporting these market caps is that payers are going to be more likely to cover therapies that have significant benefits for patients who have positive companion diagnostic results.

A lot of big pharma went after the Aurora kinase inhibitors development about 15 years ago. The program was originally developed by GlaxoSmithKline and licensed to Cancer Research United Kingdom (CRUK) to run a phase 1 clinical trial in ~36 patients. At the time we working on a foundation sponsored brain cancer program, and it turned out that children with glioblastoma and medulloblastoma could be highly sensitive to aurora B kinase inhibitors.

The foundation suggested we ask CRUK about the aurora B kinase inhibitor. After extensive due diligence by our team and especially our knowledgeable chief scientific officer we were able to obtain the molecule, but we understood we needed to develop a companion diagnostic to develop a regulatory approval pathway.

We believe NMI-900 has best-in-class properties as it binds to the enzyme for 8 to 24 hours compared to the standard 30 minutes, so we had the chemical advantage in pharmacodynamics and needed to dose less often.

We have seen a number of precision medicine companies achieve significant returns for their shareholders in the M&A space. We believe NMI-900 is a the best-in-class drug that can bring similar returns, but we don’t yet have the institutional financing behind us at this point. We decided to turn to individuals because the program is relevant to patients with AML and the key opinion leaders who are prepared to run our trials.  We already have 15K doses ready to go into the clinic. Our Board and I think it important to build a financing environment that can attract a number of individual investors using first RegCF and eventually RegA+.

The RegCF raise is our first public raise. We are also raising Series B institutional round in order to run the clinical trials and manufacture more drug which is discussed in our SEC filings. With the RegCF running parallel to the Series B, we are hoping to build individual investor awareness so in the future we might be offer shares through the RegA+ process. Once we complete the RegCF, we’ll work through audit requirements and chose the most effective platform for our future offerings.

The Series B we are running as a traditional RegD. The RegCF is a way to tell our story, whether to high networth individuals or to other individual investors. The board has set up a RegD convertible note for the high networth individuals while the RegCF is open to everyone.

Being so relevant patients with AML and in some cases to family members who have lost loved ones to this awful disease, it’s important to offer the opportunity to participate financially to individuals could potentially become some of our most important voices.