Q&A with Mark Berger, M.D., Genprex’s Chief Medical Officer

Dr. Mark Berger is a senior executive with 25 years of biotech and pharmaceutical company experience in the development of oncology therapeutics. He joined the Genprex executive team in September 2021 as its Chief Medical Officer. Dr. Berger shares a bit more about his background, experience and what excites him about Genprex.

Q: Dr. Berger, you have previously held the title of Chief Medical Officer and several other titles in drug development programs. Can you tell us a little bit more about your approach to drug development and how that experience will be beneficial for your new role at Genprex?

Several years ago I published an article in the Journal of Clinical Oncology in which I introduced the concept that drug development is like raising a child. And I still think that’s true in many ways. One tries to make the best decisions for the development of the drug, just as you do for your child. And both have an element of unpredictability, so you make the best decision you can, gather some data, and then adjust course. And you grow attached to each drug, hoping that it will ultimately make it to approval, much as one suffers through the teenage years to see a wonderful adult emerge. Having played a major role in bringing two drugs to approval, this view of drug development provides some context to the ups and downs that are always involved in the development of a new agent.  

Q: What are some of your experiences with the design of clinical trials?

With many drugs there are critical decisions in clinical trial design that determine the fate of the drug, and if one “listens” to the drug these factors can be identified. For instance, I led the clinical team that developed Mylotarg for acute myeloid leukemia (AML). Mylotarg in many ways was a precursor to today’s targeted cancer drugs approved with only early-stage data. A major challenge was to identify a patient population sick enough to benefit from the drug, but not so sick that they wouldn’t respond to any treatment. Based on data from an early trial, we excluded AML patients relapsing early after their initial treatment with standard therapy, which was a critical choice for the trials that led to approval of the drug. Today Pfizer’s Mylotarg is approved for both newly diagnosed and relapsed CD33-positive AML.

Q: How does the laboratory work that you’ve done prepare you for clinical drug development?  

I’ve had the privilege of working both in the lab and in clinical trials with targeted cancer therapies under development, such as those inhibiting EGFR and HER2. This has given me an excellent understanding of how to translate the work in the laboratory, where one can control many variables, to the clinical trial setting, where we have much less control. But, ultimately, it’s the clinical efficacy and safety that matter.  

Q: Tell us more about your role in the development of Tykerb (lapatinib).

I was privileged to play a major role in the development of the strategy for the approval of Tykerb (lapatinib) and in the trials that carried out that strategy. Although in vitro Tykerb had EGFR inhibitor activity, it became clear early on that clinically it wasn’t an effective EGFR inhibitor. So our focus quickly became HER2 inhibition in breast cancers. A key trial showed that as a single agent it had similar activity to Herceptin – and that led to combination trials with other effective breast cancer agents. Today, Novartis’ Tykerb is an approved drug used in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2.    

Q: What can you tell us about Genprex’s Acclaim-1 and Acclaim-2 clinical trials in non-small cell lung cancer?

These are both innovative trials that take advantage of the activities of the TUSC2 protein. Most patients with advanced non-small cell lung cancer have an inactivated TUSC2 tumor suppressor gene either by deletion or by post-translational modification. These trials return TUSC2 protein activity to the cancer cells, and do so in a way that is synergistic with other drugs. In the Acclaim-1 trial, REQORSA™ is combined with Tagrisso (osimertinib), as pre-clinical data showed that REQORSA inhibits tyrosine kinases like the EGFR, which is the target of Tagrisso. In the Acclaim-2 trial REQORSA is combined with Keytruda (pembrolizumab), as pre-clinical data showed that Reqorsa activates immune cells that are synergistic with Keytruda.  

Q: Can you share any information on Genprex’s diabetes program?

Diabetes is a serious disease that can often be managed through physical activity, diet, and the appropriate use of insulin and other medications to control blood sugar levels. It is a growing health problem and people with diabetes are at increased risk of serious health complications including premature death.  Despite the effectiveness of current treatments for diabetes none are as effective as the natural regulation of insulin secretion. Type 1 diabetes is fundamentally an immunologic attack on the beta cells that produce insulin. Genprex’s diabetes program is a promising way to replace the beta cells with insulin-producing cells that will evade that immunologic attack. It works well in mice, which have the same mechanisms to control insulin as humans, and we’re looking forward to bringing this technology into the clinic where we think it’s likely to lead to a leap forward in the treatment of Type 1 diabetes.

Q: What led you to join the Genprex team?

Genprex has a group of experienced people working on innovative technologies that can be brought to bear on common diseases that at present aren’t curable. That’s a recipe for success that I’m happy to join.

Q: Where would you like to see Genprex in 5 years?

It’s always a bit risky to predict the future, but predicting the past isn’t interesting. In 5 years, I would like to see Genprex replacing the activity of multiple deleted tumor suppressor genes in multiple cancers, and having what could actually be a cure for Type 1 diabetes. That’s a lot to ask for from a small biotech company – but I believe the ability and tools to reach those goals are already present at Genprex. 

Dr. Berger’s published article, “Like Raising a Child,” published in the Journal of Clinical Oncology can be found here.