From Concept to Clinical Trial Results: A Conversation with Glen Raffel, MD, PhD, VP of Clinical Research & Development

As we continue to share results from our first clinical trial, VBP101, we checked in with our Vice President of Cl
inical Research & Development, Glen Raffel, MD, PhD, to find out what it’s like seeing this concept progress from an idea to a clinical trial where we are now seeing results in patients who have received this drug candidate.

Question: You were here from the early days of inception of the first clinical trial to test the Vor approach.  Where were you when you heard about the first patient results and how did you feel when you heard about them?

Glen: I’ve been here from the very beginning of the trial and it was so gratifying to hear the first results coming through. It’s amazing to be able to bring this concept into the clinic – taking it from what was just a hypothesis or a theory to now using it to treat patients.


Question: What have we learned from the results from the VBP101 trial so far?

Glen: The original proof of concept was that we could protect normal blood cells from a targeted agent – in this case Mylotarg – by deleting the CD33 gene. Our initial results strongly suggest that’s the case – that you can administer this drug, which normally causes blood counts to go very low and makes patients susceptible to infections and bleeding, and basically keep patients’ blood counts normal. The other important thing that we’ve shown is that the deleted gene, CD33, doesn’t appear to have a major effect within blood development and can therefore potentially be removed with no adverse effects.


Question: You work with our clinical trial investigators and study sites every day. What is most gratifying about those interactions?  

Glen: The most rewarding part about interacting with our site investigators is witnessing the enormous enthusiasm that they have for the trial and their dedication to their patients. As a former physician, I know that the standard of care treatment cannot cure every AML patient. Investigators are looking for something that can potentially help their patients, so they’re invested in testing our novel approach The other advantage in working with trial investigators is being able to tap into their wealth of experience and knowledge in the transplant field and in clinical trials to help move our trial forward.


Question: What is the most challenging part of your role and the most rewarding?

Glen: The most challenging part of my role is coordinating the process. A normal transplant is already a pretty complex process and then we need to integrate trem-cel into it without causing any delays in the patient’s treatment. So we really need to be in close contact with every aspect of patient care, and that includes interacting with multiple people within each trial site and interacting with the donor registries to make sure that we can manufacture and deliver the product candidate to the patient as quickly as possible.

The most rewarding part is getting this therapeutic candidate to the patient. We have patients that are about to undergo the long and arduous process of a transplant and they know that the odds are stacked against them even with this most aggressive of care. It’s a privilege to be able to offer hope in the form of a new therapy that has the potential to improve that process and hopefully bring the possibility of a cure much closer.


Question: What advice do you have for someone who is interested in a role like yours working in a clinical team within a biotech or pharma company?

Glen: As a transplant physician, working at a biotech company is very different than working in an academic medical institution. As an attending you’re expected to have all the answers. On the biotech side, you are part of the team and you need to listen to and work with all of the different functions and all of the different people within the company and at the clinical trial site. This collaboration is essential in moving the clinical trial forward and getting the treatment to the patient in need.


Question: How do we ensure our trials are patient-centric and how can we make sure that we are continually improving the patient experience?

Glen: I’ve found that in addition to investigators, the best source of information about the patient journey is the study staff because they have the most interactions with patients. They know what the most difficult challenges are for patients, whether it’s transportation, scheduling tests, or any other aspect of the trial. If patients are facing obstacles to participating in our trial, the study staff at the clinic are going to learn about it. And so keeping an open line of communication with this team can help us learn about and address any challenges to help us make it easier for patients to participate and get the care they need.


Question: What do you hope to see in the next 5-10 years in the blood cancer space?

Glen: What I’d really like to see in the next five-to-ten years is the ability to address the shortcomings of a typical allogeneic stem cell transplant, which uses healthy donor cells. There’s been a lot of new therapies surfacing in the blood cancer space and many of them are very good at treating, but not necessarily curing cancer. One of the advantages to allogeneic transplantation, particularly for AML, is its potential to offer a cure, but it does come with a burden of toxicity as well as a significant chance of relapse.

An allogeneic transplantation works well because it’s like a living drug. You are putting in another person’s immune system and these transplanted cells seek out and destroy the cancer. However, cancer cells can adapt and evade these attacks, so you have to give patients a drug that can help outsmart the cancer. Therapeutics like Chimeric Antigen Receptor (CAR) T cells could potentially offer a solution, harnessing the advantages of immune system to attack those cells and avoid the resistance mechanisms that can cause a relapse.