YouSaid · the spoken record

Dr. Carl June

lines on the record: 42
first: 2020-02-07
most recent: 2020-02-07
sittings or episodes: 1
sources: podcast

Every line below is reproduced as it was said and linked to the record it came from. Nothing here is summarised or generated. Directory · Search · Corrections

“I think if I had my time again, there are certain things I would have accelerated in terms of my advisor. Don't wait for an issue to arise before you think, hey, you know what, I got this problem. I should try and find somebody that has an external lens to this. And it's where the humility piece has to come in. You cannot know everything. Even your team cannot know everything. So then how do you appoint the right directors to your board who bring different skill sets and advisors and accelerate all of that thinking three times faster than I've done it the first two times? So agility, tenacity, again, not giving up, the network that you have to create as an entrepreneur in this space to really think good ideas can come from anywhere. And just staying curious constantly. I mean, the one nice thing about our field is we're competitive, but we're also very, very collaborative as well in this space. More so than you will see in other biotech spaces because there's a humility as well that we just cannot solve everything ourselves.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“The last question takeaway for our other entrepreneurs and founders. You've now twice built a product and a company that's really pushing all kinds of new limits and regulatory and policy and manufacturing and delivery and all kinds of things. What's something that you would do differently now if you were going back and doing it all over again?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“You know, T cells, they stumbled upon decoding the HIV virus and realized that this can be a great payload. And look now, rashi curing cancer with a denatured approach to HIV. So the craziest ideas come from the craziest parts of science in the world, right? Who would have thought at the time that that would be a path that 30 years later would be potentially a cure for cancer?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Curiosity, right? You have to have that, your bedrock as a company. Where is the world moving to? Where is the next best idea coming from? It's how you think about staying ahead of the curve and building that network. And opportunities arise in amazing scientific settings where you least expect them. I think also people in our world who are known as self whisperers who really have seen there, been there, done it all and have seen what works, what doesn't, institutional memories are really important thing. They've got founders like Jim Riley, Carl June. You know, they first started off this field in HIV. They were actually trying to find a cure for HIV with”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“So the first generation of car came out of Novartis. The second generation of car tea is coming out of companies like TeamUmunity. There was a reason why the second generation didn't come out of Novartis. In other words, that you started a new company to go after sort of the next horizon. How do you make sure that the third generation of car comes out of Team Unity and not out of a new code that hasn't been imagined yet?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“From an actuarial perspective, right? How am I going to manage a business in this area? So part of it is owners on companies like us to be progressive and be creative and have the engagements earlier because it is a brave new world. Nobody has the magic answer here. So the earlier you get into dialogue payers and advisors in that setting, the better off we're going to be for the sake of patients and for the company as well longer term.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Pay for performance kind of models, you're going to see, I think, variations in that and versions of that. At the same time, the cost of goods of these products is coming down, be it gene therapy or cell therapy. It's a math problem, an engineering problem. And in the next five years, that'll improve. But payers, you know, if you look at a medical director in Etna United, whatever, they have a finite pop. They want to know in four or five years' time what am I going to be dealing with, right? They're getting so much better now at engaging with companies like us to forecast and think.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Okay, when you fully loaded cost, you add it all in, right? So you are pricing a product at $450,000, $425,000 of Kim Raya after rebates and discounts, whatever that is, right? You can figure out what that number is going to be roughly. You're still getting pretty good value when you think about it. I think the biggest thing for the payers was and still remains for cell therapies or gene therapies, you know, anything where there's a price tag that is higher because of the cost of manufacturing, for example, is that don't burden us with a one-time upfront cost for your therapy. We understand that you spent a lot of money in R&D, but this whole notion that we're going to be able to discharge our cost up front as a big ticket item, I think that's a thing of the past. And there's precedent outfits. And you've seen precedence now with innovation coming through in terms of reimbursement.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“It's a really good point. So, I think for the leukemias for children, it was a no brainer. It happened. If you think about it relatively quickly in the US because it was so compelling, right? So what's your standard of care? Your standard of care is a stem cell transplant for a kid with leukemia. So cost of a stem cell transplant, believe it or not, is $750,000 to $1.3 million, depending on your zip code.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“the AI and adjacent thinking to be blended into the cell journey and the patient journey and then the commercial journey. The revolution started in over yet and there's a couple more wins that I think we're going to see in the next couple of years in the T-cell engineering space.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“I think the curves will pick up. It just took longer for the uptake for a specialty product to be introduced. And hindsight, maybe there were certain things we could have done a lot earlier. There's a finite amount of resource investment you can make at certain pivot points within the life cycle of a product. But I'm pretty optimistic that the players that are going to be in this space are going to double down and increase the actual spend that's needed to really make these products successful. Because at the end of the day, none of us are in this business to break the healthcare budgets of any country. We also know we have a challenge because the products are expensive to develop. I think over time, and we've already seen this, the cost of goods have come down. We're one or two engineering steps away from some radical optimization of these products. We are going to need access to large amounts of data. We are going to need the”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“I mean, you've got to think about how physicians are going to get paid. How does a healthcare system make money out of this? What's the cost of infrastructure built? Are they going to actually invest in a stem cell lab? Are they going to invest in the logistical wiring? And at the same time, do clinical trials and also be a commercial center. So I think people underestimated the complexity of what it would take. But at the same time, nobody's disputing the stellar clinical results that you get.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Absolutely. People bringing in different baggages, right, from a cultural perspective. The teaming in our world is so different because you have to integrate what is traditionally clinical thinking with manufacturing science thinking in our world that processes the product, right? That's a very different proposition.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Absolutely, absolutely. And then the next phase of the people side really came in when we had to instill discipline process, building our quality systems, starting to write protocols, starting to really gear up for regulatory guidances, submitting INDs. And sometimes you get people on the bus. Then you get to figure out, are they on the right seat on the bus? Because you hire a utility players, right? But you also need specialist players as well. So, how do you move them around the seats on the bus? Like, should they have got on the bus? Hopefully yes. Then sometimes you realize, well, you know, this person may be better in this seat versus that seat. So we went through that phase as well.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“That's a really, really important trait in startups because there's no room for insecurity. You have to have huge self-awareness about what you know and what you don't know. And time's on your side. Now, it weighed heavily on me, the letters and Facebook postings I got from patients and their families in my former life. The patience we needed to treat have tried absolutely everything. The sense of urgency was there as well. For the first 12 months, it was, oh, we needed at that time to really secure the operations of the company. There were many times actually the company should have died. For example, there was IP that maybe wasn't what we thought it was before. You know, there were platforms that maybe the experiments weren't reading out the way they thought they would. It all worked out. But during that phase, I never knew I could be so tenacious because I'd tasted such huge success in my former life to now do this again and think, oh my God, could we really fail?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“You know, many colleagues who came on board had experienced malignancy themselves, or they'd lost a loved one or loved ones in many cases. So it becomes very, very personal. In a small company, you have to phase and stage your hiring. You can't just do a scattergun approach, right? Getting a high-performing team set up quickly where you buffer each other's weaknesses but play to each other's strengths.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Clearly, the speed with which you have to recruit is a very different pace, right? I mean, within the Nevadis world, it was fast because we went from two people to within six months having 400 people. But literally we lifted and shifted groups out of different functions in. Sometimes it had a choice, sometimes they didn't. But in the startup world, you really are relying on your network very heavily, but also really digging in quickly about people who fit really well in big pharma may not necessarily work out in startup situations and small biotech. So really understanding what is the motive of that individual. I mean, we get out of bed thinking about T cells. We go to bed at night thinking about T cells.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Oh, there's huge differences. Let's talk about the talent. So I quickly brought on board a very good colleague of mine from Nevada, Michael Cristiano, and he is the resident deal maker when it comes to everything sign gene therapies. So between the two of us, we'd actually had a cultural sense of what we had built previously and the essence of what we needed to keep, but what we needed to pivot to.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Novartis, Kim Raya, the first Car T product, was going after leukemia's lymphomas, which is about 10% of all cancers. You're going after the other 90% plus. So you're going after colid 10 times the market with a tenth of the team today. There's something fundamentally different about how you build a startup company from scratch versus a startup company within a large company that you had in Novartis.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“How do we get these therapies into patients earlier in their cancer journey, if and when it's appropriate for them to be treated with these kinds of therapies? And what needs to happen from a product standpoint to enable that?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“There's actually ways where you can target the outer casing, if I can call it, of counter, and kind of make a dent in that armor to allow payloads to go in. So payload delivery is another key factor, right, that's changing the way we think about liquid to solids. So all these modules now, the lessons learned from hematological malignancies now pivoting towards solid tumors, these principles are going to be really important, not just for companies like us, but for the entire field.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“That multivalency, as we call it. And in certain cancers like glioblastoma, we know we probably have to attack three, four different kind of surface marker proteins for patients to get a benefit. Then there is the engineering component of getting these cells to power on. So if you think of the engine of the cell, how do you really give it more choke so these cells really power up and co-stimulate? How do we armor these cells better to help them overcome immunosuppression? Because Mother Nature's one of the things that she's done an amazing job of is actually giving cancer privilege, right? And there are various ways in the system that cancer cells trick the human body. One of them is immunosuppression. So we now have the capability through gene editing, for example, to overcome that or through armoring of cells, which was not possible before.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Yeah, so let's break it down. So, how do T cells actually bind or stick to a target? Think of Velcro, right? So when Velcro attaches, the idea was that what you actually want is that Velcro never to come off. It sticks permanently really well. And that was known as high affinity, especially in terms of antibodies. And people realized, actually, that's not such a good idea because you actually get off-target effects. So you actually get something sticking where it shouldn't. There's a problem. So then this maturing of something called affinity tuning happened where it's the Goldilocks thing, right? Not too hard, not too soft church, the right amount where you get a T cell touching and activating but not totally binding. I think that's been a bit of revolution in terms of T cell engineering thinking. Then it's actually developing multiple warheads, so actually targeting more than one protein, abnormal protein or antigen.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Exactly to increase the functionality so you can go across different and more complex cancers. So going from liquid tumors like the lymphomas, like the leukemias, into solid tumors. I want to talk a bit about how you think about what needs to happen for you to bring the cost down, what has to happen from an engineering standpoint for that to happen.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Can I ask you a question around the technology and how you're going to build out your product pipeline? A lot of that's going to hinge on how you can essentially engineer cells for increased and expanded functionality. Sure. So one simplistic way to think about this is, you know, in CAR T, It's an oversimplification to compare it to software, but I will. is built on the previous generation in some ways. And you can swap in modular components.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Grown startup. So team immunity is a T cell engineering company that's focused on curing cancer. We're doing this by developing therapies in the form of either CART Ts or TCRs, T cell receptor technologies, and mainly going down the road less trodden when it comes to the tougher kinds of cancers that are mainly in the solid tumor space as opposed to hematological cancers, which there have been great successes in, still an unmet need. But there's an even huge, huge, bigger unmet need with patients with solid cancers, which is where we really want to focus.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“You know, once you've touched success in terms of curing a patient, and I use that word very carefully because as a physician, you always think twice about you're really curing somebody, when you've done that with a product, it changes your whole perspective about medicine and where the world could be. If you have the right team behind you, if you have the right culture behind you, and if you have the right platforms and technologies.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Was not easy. It was actually developing products in a different way against the paradigm. So in our world of drug development and product development, there's a very well-established cycle of how you do things. It's memorialized with the FDA that's guidances, et cetera. But try developing something that regulators have never done before, or companies have never done before. In my career, I never thought I'd work on something that could be curative. I worked on things that could help people, they could improve their health. I worked on many things that didn't do anything for patients. Products failed.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Reagent? Do we need to stimulate the cells in a certain way? All of that repeat learning. That can only happen in a full stack company. In order to be able to really maximize and create great products, we decided to own that process ourselves. So can you imagine that if we see success in a clinic and we don't have the manufacturer to go in hand, I kind of feel that's unethical. In terms of the breakthrough speed with which science is evolving, but not being able to manufacture the product would be such a shame”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“And I think the more and more you see where the world is moving to and you look at the personalized nature of what we're doing, whether these are current generation products or off-the-shelf products in the future, that ecosystem being understood from the patient journey, the cell journey, cell logistics to your point, adverse event management. And as you think about the interface of tech for the future, which is going to be required here, whether that being diagnostics, whether that being management of patient, patient selection, or whether you're looking at blockchain, for example, in terms of secure chain of identity, because look, if I'm taking your sales, you want to guarantee I'm giving you your sales back right. So there's a whole security apparatus in this and that people just don't consider when they first get into it. If we didn't have that pillar of manufacturing, if we didn't have the research engine, if we didn't have the ability to learn from each patient that we manufactured, what's working well, do we need to add a bit of this?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“So, you have to be able to manufacture this therapy. You've got to be able to manage the logistics that go from patient to the provider, from the provider to the manufacturer, back to the provider, back to the patient. What you call the vein to vein logistics. So is there really any other way to do this but to be a full stack or fully vertically integrated company if you're going to commercialize these types of therapies?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“To scale. If I go back to 2013 literally, we'd be in the size of a room like this podcast room and literally we would have tubes and bags hung on the wall. It was literally our sort of brainstorming war room of how do we take this process from an academic open process, closer manufacturing meaning lock it to good manufacturing practice standards, process development, analytical development, vector scientists, and technical operations personnel are working around the clock. So again, very different way of practicing medicine, right? This was like the Wild West in some ways in the early days, but we did it and we learned a lot through that process. We acquired our own manufacturing facility because we're not in the business of just creating product for Chronic Sake.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“That's persistent and durable cure. We hope that they remain in this state where these cells are constantly in surveillance in the body. So should a signal arise of an abnormal protein, these cells can then attack it? So I've given you a sense of the cell journey and the patient journey. Now you think about that creating a product around that. It's a whole new area of medicine, right?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“So you then go through that process and hopefully by three, four days you're seeing that window of is this patient really responding? If you don't see the cytokine storm, it means the product's not working. Interesting. We actually look forward to an adverse event, which is really weird in medicine, because if you don't see it, you know the product's not working. 28 days later, when the patient is better, the fevers subside, and you do a bone marrow biopsy, you do various blood tests, and you see over 90% of kids initially in the trials got complete remission after 28 days. And there are children out now”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“The cells are given as one infusion. And what you typically see is a spike in the patient's fever. These cells start to multiply very, very rapidly. And at the same time, they're pushing out massive amounts of protein. And they start to literally attack the cancer wherever they see it. Cancer, when it's destroyed, releases a lot of toxins. And that manifestates itself in something called cytokine release syndrome. It's like a storm in your body. It's like a storm. That's what they call the cytokine storm.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“And you cross your fingers and toes because sometimes they don't grow. These are cells that have become fatigued and they just don't have that oomph, that energy that's needed to grow. Then you have to harvest out the cells once they've grown. Then you have to freeze them. Then you have to ship them. A mild chemotherapeutic regimen is given to the patient. We kind of call it conditioning. And conditioning is that you want to get the patients at a certain state that you create space in their body for them to receive these cells and the cells to expand.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“So you've harvested their cells, you then go through a process of seven to ten days where you have to re-engineer those cells. Those cells go through a process of cell selection, so the right cells are extracted. They're then excited by a certain degree with certain technologies that basically make the cells in a receptive state that you can then deliver a Trojan horse into it. The Trojan horse is this payload that we deliver of the genetic code that expresses this new surface marker called a cart on the surface of the cells. You then go through a process of three days watching these cells. Are they going to grow?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“There's more chemotherapy is provided. But then there comes a point where these patients become what we say in the oncology world, refractory relapsing. So they're refractory to any further chemotherapeutic agent being given to them. And they're relapsing because the disease is worsening. And so that patient is then brought into have their blood drawn to see, do they have that right surface marker that you could create this engineer therapy for? If they express something called CD19, then we basically harvest out their T cells in a process called aphoresis, whereby patient's blood is withdrawn through a machine and it filters out the white blood cells. Those cells are then taken and they're shipped to a central manufacturing facility in the case of the University of Pennsylvania they actually have their own manufacturing capability.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“And that number is a specific cancer antigen or a protein that's an abnormal protein on the surface of cancer cells. And we're able to get these T cells to then actually become killing machines in some ways, whereby they identify an abnormal protein on the surface of a cell and they go and attack. So let's do what I call the patient journey in the cell journey. So I'm going to take a profile of a child with leukemia. You have a child of the age of three or four. start getting bruising they go to their family practitioner they do a cbc they look at a blood count and they have massive leukemia in terms of their y cell elevation child gets rapidly assessed they start chemotherapy and great news they respond and most kids were leukemia respond really well to chemotherapy two years later there were routine follow-up and boom the next thunderbolt comes in unfortunately they're starting to now get leukemic breakthrough”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“Of it like a GPS system in cells that we've been able to engineer, we take cells from a patient, we engineer them, we give them back, and those cells detect cancer and destroy them. Best analogy as I can give is like a SIM card into the T cells. That SIM card that gets expressed on the surface of those T cells is very unique. It only dials one number.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“And that's where the chimera comes in. So chimera was an ancient Greek mythological figure that was a hybrid, I think, of a female lion, a dragon, and a serpent or something. So the whole idea being, could you combine and create a blend of something with the idea that you could create therapies around it? And the nub of the therapy really involves taking a patient C-cells and we re-engineer those T cells.”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source
“So Cart T is also known as chimeric antigen receptor therapies. Nature's biggest gift that we were given in terms of protecting us from disease is something called T cells. They're a subset of your blood cells that are called white cells. White cells typically prevent infection disease. So they are always surveilling and protecting you. A B cell produces antibodies. A T cell actually hones in and gobbles up peptides and abnormalities that are circulating in the system. And the idea was, could you combine the features of a B cell and a T cell together?”
2020-02-07 · a16z Podcast · Building the First CAR T Company · IDENTIFIED FROM THE TRANSCRIPT · source