One CEO, Two Pharma Companies

Many early stage biopharmaceutical enterprises diversify their drug development portfolios in a particular disease indication and find efficiencies in development; for example, applying the same molecule to different disease indications. However, one CEO is trying a different strategy by managing two different biopharmaceutical enterprises in two different disease indications. Hugh McTavish, CEO of Squarex and IGF-Oncology will discuss his perspectives on running both enterprises and the medical products each is developing.

Moe Alsumidaie:  What Are Squarex and IGF-Oncology?

Hugh McTavish: IGF Oncology is developing a targeted chemotherapy drug that binds to a receptor that is over-expressed on cancer cells. It's more effective and has fewer side effects than conventional chemotherapy.

Squarex is developing a topical drug that prevents cold sores and is unique in several respects. Currently, there's nothing on the market for the indication of preventing cold sores or herpes labialis outbreaks in people who have frequent outbreaks. It is also applied to the arm, not to the lip like the current standard of care.

MA: Managing two biopharmaceutical enterprises in two different disease indications must be challenging. What are those challenges, and how do you find efficiency/overlap in both enterprises? How are the companies different?

It is largely the same team for both companies. I founded both companies, both have the same Chief Medical Officer, Dr. Arkadiusz Dudek, and the same clinical trials manager and clinical trials monitor. I do patent work for both companies, and we have our own laboratory that does work for both companies.

MA: Is this a treatment for people who are already infected with herpes simplex virus (HSV) or is this a vaccine?

HM: The FDA makes a distinction between treatment and preventative therapies. The drugs on the market, like VALTREX® and ABREVA®, are treatments, which are aimed at shortening outbreaks once an outbreak has started.  Our drug is a preventative therapy that reduces outbreaks for people who are already infected with HSV, so it is intended to make it less likely that you're going to get an outbreak. There are no drugs approved for the indication of preventing outbreaks.

MA: Can you discuss SQX770 and its mechanism of action? How does it differ from existing therapies on the market?

HM: We've had a couple of publications on this drug. The first one, our Phase I clinical trial, was placebo-controlled and showed efficacy in preventing cold sore outbreaks as a primary endpoint after one dose on the arm, extending the time for new outbreaks from 40 days in the placebo group to greater than 120 days in the drug treatment group. That was in a population of people who had six or more outbreaks per year.

We did another mechanism of action study in people with six or more outbreaks per year. We studied three groups of people who were all positive for antibody against HSV-1: people with zero outbreaks, people with one or two outbreaks, and people with six or more outbreaks.

The people with few outbreaks had better immune control, and their blood cells proliferated more against the virus than people with multiple outbreaks. Two months after one dose with our drug, the patients with frequent outbreaks became more like those with good immune control with no or few outbreaks in every single respect. Their white blood cells proliferated more against the virus, and they expressed more interferon gamma and less IL-5. So, the drug seems to train their immune system to fight the virus more effectively.

MA: Is this a preventative drug that’s to be taken daily?

HM: No. We dosed once on the arm, and that prevented or extended the time for new outbreaks to 120 days. I assume people will need to be dosed again, but it's not a daily regimen.

MA: I understand that you had non-Hodgkin’s lymphoma. Did this play a role in the development of the IGF pipeline and in particular the IGF-MTX drug?

HM: Yes, I had non-Hodgkin's lymphoma and developed this compound as an outgrowth of my treatment. I have a PhD in biochemistry, but my research had not been in cancer until I got cancer. After reading several journal articles I chose an unusual treatment, and then I invented our targeted IGF-MTX drug as an improvement on that treatment. I am also a patent attorney, so I wrote a patent application for it as well and started IGF Oncology. IGF is seeking regulatory clearance for a different kind of blood cancer called myelodysplastic syndrome or MDS, but we feel our drug would also be useful for Non-Hodgkin’s lymphoma.

MA: Does IGF’s therapy use similar mechanisms of actions to target those two different types of cancers?

HM: Yes, it is a form of methotrexate, an old chemotherapy drug that is covalently attached to a protein called insulin-like growth factor-1, for which IGF Oncology is named. It's our patented variation of insulin-like growth factor that binds to the IGF-1 receptor, which is overexpressed in cancer cells and allows more drug to reach the cancer cells and less to the healthy cells. Since the IGF receptor is overexpressed in numerous cancers, we don't think that it's going to be limited to MDS, but that appears to be a useful disease target for this drug.

MA: How does this mechanism of action spare non-cancerous cells and reduce the adverse effects that people would typically experience with other cancer treatments?

HM: t doesn't entirely spare the non-cancerous cells. The IGF receptor is expressed on healthy cells as well. However, we get more drug to the cancerous cells and less to the healthy cells. Free methotrexate goes everywhere and doesn't distinguish between attacking cancerous and healthy cells. It exerts its selective toxicity for cancer cells because, like all chemotherapy, it interferes with DNA replication. It's toxic for cells that are actively dividing, which tend to be the cancerous cells, versus cells that do not divide so fast.

MA: Several companies are taking older therapeutics and shifting the application of them. Why choose this route and why not create a new molecular entity?

HM: It is a new molecular entity because it's a new covalent conjugate of the methotrexate to the IGF. We hope to get approval through the 505(b)(2) route using the data and publications on methotrexate itself to establish safety and efficacy. That may offer some advantages and make for a faster drug approval since we already know the side effects on methotrexate.

MA: All stakeholders are going to be interested in drugs that are less toxic or more efficacious. What advantages do you anticipate this new therapeutic will bring to patients in terms of safety and efficacy compared to standard of care?

HM: We've had very encouraging results in the Phase I MDS study. We are still in drug escalation, and it worked in the first two patients we treated in a clinical trial at the Mayo Clinic. We are encouraged by that and think we can improve efficacy. We also have lower side effects, which is why we chose MDS. We found no decrease in blood cell counts in our first clinical trial in patients with various solid tumors, which is the most severe side effect of chemotherapy. So, we can have better efficacy with lower side effects, which is vital for patients undergoing chemotherapy. I've known a few people, including myself, who have gone through chemotherapy and it's awful. However, if we can alleviate that suffering and lower side effects, it would be a significant improvement in the patient’s quality of life.

MA: Could you tell me about some of the milestones you expect in 2019 and 2020 for IGF Oncology and Squarex?

HM: For Squarex, we finished a Phase II trial, and we want to do another small clinical trial as well as some toxicology testing in 2019. I'm hoping to start our pivotal Phase IIIs by the end of 2019 or early 2020. Those are the significant milestones for Squarex. For IGF, we want to finish the current Phase Ib, the dose escalation portion for MDS with IGF methotrexate, and then start a Phase II that we would get approval off of the Phase II clinical trial.

Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical.