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Navigating Cell and Gene Therapy: Insights and Challenges with Dr. Bruce Levine · Lab to Lives

• 0:21
  Speaker 1: Welcome to Transformation in Trials.
• 0:23
  Speaker 1: This is a podcast exploring all things transformational in clinical trials.
• 0:27
  Speaker 1: Nothing is off limits on the show and we will have guests from the whole spectrum of the clinical trials community and we're your hosts, ivana and Sam.
• 0:35
  Speaker 1: Welcome to another episode of Transformation in Trials.
• 0:40
  Speaker 1: Today we're going to focus on the topic of clinical research in cell and gene therapies, and today in the studio with me I have Dr Bruce Levine.
• 0:48
  Speaker 1: Bruce, do you mind telling us a little bit more about yourself?
• 0:52
  Speaker 2: Hi Ivana.
• 0:53
  Speaker 2: So first, thanks very much for the invitation to speak with you.
• 0:57
  Speaker 2: I serve as the Barbara and Edward Netter Professor in Cancer Gene Therapy at the University of Pennsylvania.
• 1:05
  Speaker 2: I'm also the immediate past president of the International Society for Cell and Gene Therapy.
• 1:12
  Speaker 2: My background is I'm trained as an immunologist and I'm the founding director of Orso Manufacturing Facility, the clinical cell and vaccine Facility here at Penn.
• 1:28
  Speaker 1: Well, you are the perfect guest for discussing this specific topic and I'm very excited to have you in the studio here.
• 1:33
  Speaker 1: So, Bruce, setting the stage for us, could you explain to our listeners what cell and gene therapies are?
• 1:42
  Speaker 2: Well, there are many different flavors, but the essence is cell and gene therapies aim to replace or enhance a biologic function using modified of approvals recently to speak about, namely gene modified T cells, gene modified stem cells.
• 2:01
  Speaker 2: There are many other products in development and we can cover a range of aspects.
• 2:24
  Speaker 2: I think we can cover a range of aspects, I think, but I think what your audience is looking at is how are cell and gene therapies different compared?
• 2:38
  Speaker 1: to conventional drugs?
• 2:38
  Speaker 1: Right, absolutely.
• 2:39
  Speaker 1: And also especially, how is it different to do clinical research in cell and gene therapies?
• 2:44
  Speaker 1: Also, especially how?
• 2:47
  Speaker 1: Is it different to do?
• 2:48
  Speaker 2: clinical research in cell and gene therapies.
• 2:49
  Speaker 2: Well, I mentioned modifying cells and growing cells.
• 2:52
  Speaker 2: In these cases, what identity?
• 3:12
  Speaker 2: And then we're administering those cells.
• 3:16
  Speaker 2: Now that sounds simple in practice but in reality it's quite complex.
• 3:22
  Speaker 2: It's quite complex because we have a manufacturing that often is a lot size of one, because we're moving from the patient themselves and we're delivering back to the patient themselves.
• 3:36
  Speaker 2: So that has implications beyond lot size in the characterization, in comparability, in the time to deliver the product to the patient.
• 3:50
  Speaker 2: And because of all these complexities and being at the very early stages of development, it's been said that the chemistry, manufacturing and controls section of an investigational new drug application, or CMC, for existing traditional drugs the composition of the IND may be 80% clinical and 20% CMC.
• 4:17
  Speaker 2: Peter Marks at the FDA and others have said in cell and gene therapies it's actually reverse.
• 4:24
  Speaker 2: The idea is about 20% clinical and 80% emphasis on the CMC.
• 4:33
  Speaker 2: That is a stark difference, and I'm also thinking this must mean something for the proximity of the patients and the research center where the drug is actually being produced.
• 4:49
  Speaker 2: Yeah, absolutely, because we are sourcing material from the patients.
• 4:55
  Speaker 2: Where is that occurring?
• 4:56
  Speaker 2: It's occurring at the hospital and in clinical trials.
• 4:59
  Speaker 2: Manufacturing may occur at the hospital Often it does or an allied facility.
• 5:06
  Speaker 2: For the commercial products there are centralized manufacturing and then delivery back to the hospital.
• 5:13
  Speaker 2: So we're thinking about these logistics of drug production.
• 5:18
  Speaker 2: Where you get the raw material is quite different.
• 5:22
  Speaker 2: The drug product originates from the patient.
• 5:27
  Speaker 2: Of course, there are other reagents and materials that are obtained and the viral vector, for example, the culture, media but in essence the product originates with the patient.
• 5:43
  Speaker 2: It's modified and then delivered back to the patient.
• 5:47
  Speaker 2: Now, some have spoken about doing this more locally, but because of the complexity, there is a high bar.
• 5:57
  Speaker 2: There is a certain level of expertise that is required to be established and to be maintained as well.
• 6:08
  Speaker 1: I'm curious what does the proportion of the CMC in the IND?
• 6:14
  Speaker 1: What does that mean for how new drugs are evaluated by regulatory authorities?
• 6:21
  Speaker 2: Well, it's all important, and yet there are many unknowns.
• 6:25
  Speaker 2: And, for example, when developing a new product, how do you think about potency?
• 6:34
  Speaker 2: Well, these cell products and gene-modified cell products, in large part, or virtually all of them, are living drugs, which means that they're going to, after infusion, divide and differentiate.
• 6:54
  Speaker 2: So if you're measuring potency at a point in time of formulation, what does that mean for what that cell, what that drug, will eventually become?
• 7:07
  Speaker 2: And so we can measure things ex vivo in the laboratory.
• 7:13
  Speaker 2: But the correlation to clinical impact and clinical responsiveness is still, I would say, somewhat tenuous, and what we have to do is correlate backwards.
• 7:27
  Speaker 2: Okay, so if we have clinical responses, what are the indicators of that clinical response?
• 7:33
  Speaker 2: And then how can we track that back to something that we can perform ex vivo?
• 7:40
  Speaker 2: But I'll say that there are many, many challenges to doing that and to saying that we have a potency assay that can predict clinical responsiveness.
• 7:57
  Speaker 1: I'm wondering have any of these dynamics been the reason for why we do need the International Society for Cell and Gene Therapy?
• 8:04
  Speaker 2: reason for why we do need the International Society for Cell and Gene Therapy.
• 8:08
  Speaker 2: Well, absolutely, and there's a lot of things that IACT does.
• 8:14
  Speaker 2: And let me just take a step back and say that the mission of the International Society for Cell and Gene Therapy is to drive a clinical translation of cell and gene therapies worldwide.
• 8:26
  Speaker 2: So we are a global society.
• 8:29
  Speaker 2: We're composed of clinicians, regulators, researchers, technologists, industry partners, and we're all engaged in this vision to translate cell and gene therapy into safe and effective therapies to improve patients' lives.
• 8:49
  Speaker 2: So we are very much focused on the preclinical and translational aspects, and it's only by understanding that and meeting to discuss what are the latest advancements that we can develop these innovative treatments.
• 9:08
  Speaker 2: So altogether, we have about 3,000 members I think heading to 4,000 this year and we represent about 65 countries currently, although I expect we'll be bringing on some more countries.
• 9:26
  Speaker 2: So I've made the analogy that because we're composed of three sectors right, scientific, with a strong representation from academia, regulatory and quality operations, and the industry sector.
• 9:47
  Speaker 2: You could think of that like the Rosetta Stone, right?
• 9:50
  Speaker 2: So the Rosetta Stone says the same thing in Greek, in Egyptian, Demotic or language of the common people, and in hieroglyphics.
• 10:03
  Speaker 2: So you need to be proficient in all three of these languages.
• 10:08
  Speaker 2: So why was that stone written in three languages?
• 10:14
  Speaker 2: To reach all people.
• 10:15
  Speaker 2: But at IACT we have all people gathered together in our society, gathered together at our meetings.
• 10:24
  Speaker 2: Because you need to be proficient, or at least aware of the implications in all three of these sectors to translate cell and gene therapies.
• 10:37
  Speaker 1: And what is the potential that you are seeing?
• 10:40
  Speaker 1: What could the cell and gene therapies do for patients?
• 10:54
  Speaker 2: Well, what we're seeing in the approvals of CAR T-cell therapies and gene-modified stem cell therapies for sickle cell and thalassemia is the potential for long-time cures, certainly significant clinical remissions with a one-time treatment, and in some cases this is without additional drug therapy.
• 11:16
  Speaker 2: In many cases they may need some additional therapies, but think about that from the patient perspective.
• 11:24
  Speaker 2: Therapies, but think about that from the patient perspective.
• 11:30
  Speaker 2: They have been on lifelong medications sickle cell and thalassemia or failing a regimen after chemotherapy regimen in the case of leukemia, lymphoma myeloma and here's a one-time treatment of their own cells, which itself is empowering right.
• 11:47
  Speaker 2: So one-time treatment to have a significant and durable clinical effect.
• 11:59
  Speaker 1: That is a potential worth pursuing.
• 12:01
  Speaker 1: I want to shift gears a little bit and talk about this statement that the FDA recently issued, where they were investigating serious risk of T cell malignancy.
• 12:13
  Speaker 1: I'm curious what is the ISCT stance on this?
• 12:19
  Speaker 2: Yeah.
• 12:19
  Speaker 2: So first let me set the stage and say what we know.
• 12:24
  Speaker 2: So first let me set the stage and say what do we know.
• 12:25
  Speaker 2: This was a fairly unusual announcement from the FDA.
• 12:30
  Speaker 2: Last November they announced that there was an investigation into cases of T cell malignancies, or so-called secondary malignancies, post-administration of CAR T-cells.
• 12:48
  Speaker 2: Well, what else do we know?
• 12:50
  Speaker 2: There are 22 cases of T-cell malignancies out of 8 to 10 or 11,000 in the FDA voluntary reporting databases.
• 13:01
  Speaker 2: There are three cases in about 11,000 reported to another voluntary database, the CIBMTR.
• 13:10
  Speaker 2: There are cases in five out of the six approved CAR T-cells that appear between one and 19 months post CAR T-cell treatment.
• 13:20
  Speaker 2: Well, those databases are voluntary.
• 13:23
  Speaker 2: T cell treatment Well, those databases are voluntary.
• 13:24
  Speaker 2: There have been 27,000 patients treated in the US, about 35,000 worldwide, so more of those other patients who have not been reported.
• 13:37
  Speaker 2: It's also been stated that some of those 22 cases are CAR positive, which means that some are not.
• 13:45
  Speaker 2: So if some are not, then how can you make the link between the CAR and the development of a T-cell malignancy?
• 13:55
  Speaker 2: We also don't know if the CAR gene in those cases that are CAR positive is it a passenger or is it a driver.
• 14:05
  Speaker 2: In other words, would these patients have developed secondary malignancy anyway?
• 14:11
  Speaker 2: In some sense there is what's called an immortal time bias, which means patients who are eligible for CAR T-cells, ordinarily they would have a very short lifespan because they don't have available therapies.
• 14:28
  Speaker 2: So you would not see the development of these secondary malignancies.
• 14:33
  Speaker 2: And to that end, there has been some talk of looking at well.
• 14:37
  Speaker 2: Looking at well, can we find a similar cohort of patients who never received CARs and compare to those that received CARs?
• 14:50
  Speaker 2: And is the rate of secondary malignancies, in particular these T-cell malignancies, any different?
• 14:56
  Speaker 2: And there was an investigator at the Mayo Clinic, rafael Fonseca, that has attempted to do that by looking at billing codes.
• 15:05
  Speaker 2: This is something he has published on Substack.
• 15:09
  Speaker 2: I didn't know that you can publish preprints on Substack, but apparently now that's a thing.
• 15:17
  Speaker 2: And the bottom line is again, in small numbers.
• 15:21
  Speaker 2: He did not see a difference in the occurrence between patients who received CARS and who did not.
• 15:28
  Speaker 2: So what we need is improved reporting.
• 15:33
  Speaker 2: The databases are voluntary, but we're encouraging reporting because we can't investigate what we don't know about.
• 15:44
  Speaker 2: We need thorough investigations, right?
• 15:48
  Speaker 2: So at this stage the true nature and the frequency and the risk of that genotoxicity due to retroviral or lentiviral insertion is unknown.
• 16:00
  Speaker 2: That does deserve thorough investigation and transparency.
• 16:06
  Speaker 2: We're encouraging reporting to both voluntary databases.
• 16:11
  Speaker 2: We're encouraging patient follow-up.
• 16:13
  Speaker 2: Recommendation is that centers with expertise on cell therapy should continue to make those commercial products available to patients when this appears to be the best option possible based on the most up-to-date and confirmed safety information.
• 16:37
  Speaker 1: Why may there be a reason to not report to these voluntary databases when this is such a new area and we need to understand.
• 16:46
  Speaker 2: I think some of it is inertia that does every site know, or have reinforced, that they should report to these databases?
• 17:00
  Speaker 2: It's not required, so they may view it as optional.
• 17:06
  Speaker 2: So who takes the responsibility for doing reporting?
• 17:11
  Speaker 2: And patients may be lost to follow-up Maybe they move from the center where they were treated to another center or they're not picked up.
• 17:24
  Speaker 2: So I suppose there were a number of reasons why and, if we can go back to why did the FDA make the announcement of this investigation with so little information?
• 17:42
  Speaker 2: I think a lot of it was to encourage reporting and to encourage following the patients, obtaining samples and performing the investigations.
• 18:01
  Speaker 1: I'm curious what does this require from the medical professional deciding on which treatments to provide?
• 18:08
  Speaker 1: To understand well, what are the risks and benefits of cell and gene therapy?
• 18:14
  Speaker 2: Well, I.
• 18:18
  Speaker 2: I think, not too much has changed there.
• 18:22
  Speaker 2: We think of how to speak to patients, right about this, and there was a nice piece from Rahul Banerjee and colleagues at the Fred Hutch that published on this and colleagues at the Fred Hutch that published on this that still, the benefits of CAR-T cell therapy generally outweigh the risks.
• 18:49
  Speaker 2: At this point, causal association is possible, but there there are still many unknowns, right, so we do need to speak about this with patients in a transparent fashion.
• 19:10
  Speaker 2: But everyone that I'm speaking with believes that the benefits continue to outweigh the risks and what I've heard from the patient community is this really isn't too much on their radar.
• 19:28
  Speaker 1: Is there anything that we could do as an industry to promote more research in cell and gene therapy?
• 19:36
  Speaker 2: Well, I think, with respect to this particular issue, I've made the recommendations of the investigations.
• 19:49
  Speaker 2: But, more broadly, how do clinical practices need to evolve to accommodate the new products and products coming on?
• 19:59
  Speaker 2: It all comes down to a number of things.
• 20:02
  Speaker 2: We need more people, so we need people to be trained.
• 20:07
  Speaker 2: We need competency assessments and proficiency testing at the clinical sites In the case of multiple clinical sites for the commercial products establishing the comparability of practices, data platforms having dedicated space and staff, and there are approved products from now, a number of companies and they may come with their own platforms for training, for certifying data platforms.
• 20:42
  Speaker 2: So their efforts to harmonize the establishment of these programs and quality practices and accreditation.
• 20:50
  Speaker 2: And that's where organizations like FACT, the Foundation for the Accreditation of Cellular Therapy, come into place.
• 20:59
  Speaker 2: Cellular therapy come into place.
• 21:08
  Speaker 2: And, yes, more research research at the basic and translational phases and also research here, in this case at the correlative study stage.
• 21:13
  Speaker 2: Right, Samples from the patients in follow-up.
• 21:16
  Speaker 2: Who were they?
• 21:17
  Speaker 2: Did they have any genotoxic events from their preceding chemotherapy?
• 21:24
  Speaker 2: Maybe they were already on the road to developing secondary malignancies?
• 21:30
  Speaker 2: Right?
• 21:33
  Speaker 1: That's a good point.
• 21:34
  Speaker 1: I would be curious about your journey into this space.
• 21:38
  Speaker 1: How did you end up in the cell and gene therapy space?
• 21:43
  Speaker 2: Well, I think, serendipitous.
• 21:45
  Speaker 2: My father's a retired scientist and I had an interest in science and biology.
• 21:53
  Speaker 2: I wasn't really sure what I wanted to do to pursue that, but that it likely wouldn't include medical school, because then you're seeing patients all the time and you're not doing the research, although there are people that do both.
• 22:17
  Speaker 2: At the time that I was deciding whether or not to get a graduate school or medical school, there wasn't this knowledge or my knowledge of clinical investigation.
• 22:30
  Speaker 2: So I asked some of my professors what do you see the field in the next 20 or 30 years?
• 22:37
  Speaker 2: What is going to be the most impactful field?
• 22:41
  Speaker 2: And I got a couple answers of immunology.
• 22:44
  Speaker 2: So I also got advice from my father if you want to go to graduate school, you should work in a lab for two years to be sure you really like it.
• 22:53
  Speaker 2: Because if you work in a lab for six months and he said that's not for me or a year, well why are you going to grad school?
• 23:03
  Speaker 2: So I worked for two years at Children's Hospital of Philadelphia right over there, as a technician in the Division of Infectious Diseases, and my job was to do the immune assessment the correlative studies, if you will on patients and subjects that were enrolled in clinical trials of the vaccine for chickenpox, the varicella vaccine and then the combination MMRV vaccine.
• 23:32
  Speaker 2: And this was when the hospital was one building and you'd ride in the elevator with kids who were patients there.
• 23:42
  Speaker 2: They would be sometimes in wheelchairs with IVs or on stretchers and it really gets you thinking why are you doing the research anyway?
• 23:51
  Speaker 2: So that sparked my interest in translational and clinical research and I applied to grad school and got in at Johns Hopkins to a program called Immunology and Infectious Diseases and chose a laboratory in the hospital to do my thesis work and this was in the Division of Boneware Transplantation.
• 24:31
  Speaker 2: Well, readings for my research and thesis project I came across papers by a guy named Carl June and he was at the Naval Medical Research Institute.
• 24:36
  Speaker 2: I applied for a postdoctoral fellowship and started work on signaling and hematopoietic stem cells and T cells and how to grow T cells.
• 24:43
  Speaker 2: And then he asked me how would you like to start a lab that grows cells for patients in a trial of adoptive immunotherapy?
• 24:54
  Speaker 2: So that was that and we started a trial in HIV.
• 25:00
  Speaker 2: We're able to show that we increased CD4, cd8 counts and immune function and saw how that could be applied to cancer.
• 25:09
  Speaker 2: And he was being recruited all over.
• 25:12
  Speaker 2: One opportunity came up at the University of Pennsylvania and I said well, let me tell you why.
• 25:19
  Speaker 2: You won't have trouble recruiting me back up to Penn.
• 25:23
  Speaker 2: So that was in 1999.
• 25:27
  Speaker 2: So we just passed the 25-year anniversary of when we arrived up at Penn, in 1999.
• 25:39
  Speaker 1: Wow.
• 25:39
  Speaker 1: Well, it must also have been an interesting journey to see that whole field evolve, since you started pretty early on as it was taking shape.
• 25:49
  Speaker 2: Yeah, you know, times were different back then.
• 25:52
  Speaker 2: There wasn't this whole field of cell and gene therapy.
• 25:57
  Speaker 2: People were just starting to do these adoptive cell therapy trials.
• 26:04
  Speaker 2: Steve Rosenberg at NIH was one of them, and we and a few other groups.
• 26:11
  Speaker 2: And when you go to meetings and the ICT was just starting at that time when you go to other meetings to talk about cell therapy, let alone gene therapy, we joke.
• 26:28
  Speaker 2: Well, you'd be in the last year Day of the meeting, in the last session, in a room nobody could find, and everyone there was your friends.
• 26:38
  Speaker 2: It's a much bigger field now and we've seen the ICT.
• 26:45
  Speaker 2: For example, when I became president-elect in 2018, membership was around 1,400 or 1,500.
• 26:56
  Speaker 2: Membership was around 1,400 or 1,500.
• 26:58
  Speaker 2: And now, by the end of the year, we could have close to 4,000.
• 27:02
  Speaker 2: So that's a tremendous growth in IACT.
• 27:14
  Speaker 1: That, I think, parallels the tremendous growth and interest in the field.
• 27:16
  Speaker 1: Absolutely.
• 27:17
  Speaker 1: I am curious because it seems like this field requires deep knowledge about the CMC side of things, but also deep knowledge about the clinical side of things.
• 27:28
  Speaker 1: Are you seeing more interdisciplinary collaboration or are people specializing in both areas at the same time?
• 27:38
  Speaker 2: Yeah, absolutely.
• 27:39
  Speaker 2: And I'll make the analogy back to what labs look like.
• 27:46
  Speaker 2: When my father started his lab at the Worcester Institute and when I was there, you'd walk down the hallway and you'd have a lab and there would be an investigator.
• 27:59
  Speaker 2: And then you walk down some more and there'd be a separate room for the next investigator.
• 28:05
  Speaker 2: And then labs started to be designed with long bays and you could see all up and down the corridors.
• 28:16
  Speaker 2: But now and that's the case now in general but with cell and gene therapy you need so many different areas of expertise.
• 28:25
  Speaker 2: We have a center here, center for Cellular Immunotherapy, with 30 labs, 30 investigators looking at all aspects of cell and gene therapy, cellular therapy a lot on T cells, but also on gamma delta T cells and K dendritic cells.
• 28:45
  Speaker 2: To bring that forward need another group to take from millions of cells research reagents to billions of cells, clinical reagents to billions of cells, clinical reagents from research equipment to clinical manufacturing equipment.
• 29:01
  Speaker 2: You need the manufacturing facility, you need a quality control group to test the cell product, you need the correlative studies and then the whole clinical infrastructure.
• 29:13
  Speaker 2: So all together we're about 230, 240 people.
• 29:18
  Speaker 2: That someone very nicely described a couple of weeks ago to me I hadn't heard of it.
• 29:24
  Speaker 2: A biotech in sheep's clothing, or I say a biotech embedded in academia, but really that's what it takes is people with expertise in many, many different areas to come together to enable this translation, and that's just for clinical trials.
• 29:45
  Speaker 2: We're at a university, so we're not going to commercialize a product.
• 29:53
  Speaker 1: That is an excellent way of saying it, that you actually need to have the full complexity of a biotech within your research space to be able to deliver on.
• 30:03
  Speaker 2: And we have spun out companies from the center and then they raise funding that isn't available to us here directly at the university.
• 30:15
  Speaker 2: But they raise funding, they start a company, they move on campus or maybe somewhere else and conducting clinical trials that are investigator-initiated trials, that we can conduct the phase one trials here at Penn, and then when it's successful it can move out to the company or to a contract manufacturing organization or something else.
• 30:46
  Speaker 1: That is fascinating and also an interesting insight into how some of these biotechs actually are born.
• 30:51
  Speaker 1: Well, Bruce, as we start rounding off this episode, we always ask our guests the same question in the end, and that is if we gave you the transformation trials magic wand that can change one thing in the life sciences industry, what would you wish to change?
• 31:12
  Speaker 2: Well, I like magic wand, so I really would like one.
• 31:16
  Speaker 2: I think, and I mentioned it earlier, we need more young people entering the field and coming in from allied fields such as bioengineering.
• 31:28
  Speaker 2: We need workforce development and education and training because of that and we have a very strong effort of that now in IACT, having recently formed the IACT Institute of Training and Development, where we offer many online courses and webinars, but also in person, hands-on.
• 31:58
  Speaker 2: In addition, we have all of our committees, our 45 committees, to talk about and move forward all of these aspects.
• 32:10
  Speaker 2: We have the ANO meeting.
• 32:13
  Speaker 2: Of course this year it will be in Vancouver at the end of May.
• 32:16
  Speaker 2: We have the ANO meeting.
• 32:16
  Speaker 2: Of course this year it will be in Vancouver at the end of May.
• 32:18
  Speaker 2: We have an early stage professionals committee to really take people who are just entering the field and provide both peer to peer mentoring and mentoring from folks that have gray hair like me, and that program has expanded at a very rapid rate.
• 32:41
  Speaker 2: So I think it all comes down to this is still a new field.
• 32:49
  Speaker 2: It's growing very, very rapidly.
• 32:52
  Speaker 2: We have lots and lots of exciting science to translate into clinical trials and to develop to bring to patients through regulatory approval and commercialization.
• 33:05
  Speaker 2: So we need new experts at all levels and in all sectors.
• 33:13
  Speaker 1: I think that's a really great thing to wish for and hopefully that will inspire some of our listeners to perhaps look in this direction.
• 33:23
  Speaker 2: Yes, absolutely.
• 33:25
  Speaker 1: Well, Bruce, if our listeners have follow-up questions to you and want to learn more about both your work at the International Society for Cell and Gene Therapy or any of your other work, where can they reach out to you?
• 33:42
  Speaker 2: Well, just Google me at the University of Pennsylvania.
• 33:46
  Speaker 2: I'm also on LinkedIn.
• 33:48
  Speaker 2: I'm also on Twitter.
• 33:49
  Speaker 2: I still call it Twitter.
• 33:51
  Speaker 2: Reach out also to the ICT webpage and join, if you're not already a member.
• 33:59
  Speaker 2: And if you want a little taste, come to Vancouver for our annual meeting.
• 34:03
  Speaker 1: Awesome.
• 34:05
  Speaker 1: Well, this has been an absolute pleasure having you on the show.
• 34:08
  Speaker 1: Thank you so much, Bruce.
• 34:10
  Speaker 2: Thank you, Ivana.
• 34:12
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• 34:14
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