The Mix Tape | Special Edition – Cell and Gene Tx Journey to Commercialization: Drug development and Manufacturing

Paige Nelson:

Welcome to the Mix Tape. I’m Paige Nelson, Head of Business Development for Mix Talent. We’re excited to partner with ADVI Health to host the special edition of the Mix Tape podcast to bring together women leaders in cell and gene therapy to discuss the journey from manufacturing to commercialization, providing a forum to share experience, areas of expertise and insights for the future.
Today I’m joined by my co-host, Melissa Nocar, head of marketing at ADVI. Melissa, thanks for being here. Tell us a little ait about ADVI.

Melissa Nocar:

Thanks, Paige. As we both know, cell or gene therapy coverage and reimbursement requires a nuanced, multidisciplinary approach. It also requires deep knowledge in policy, pricing and access oftentimes alongside the right partner. ADVI Health is a trusted consulting firm and trailblazer with critical commercialization launch preparation for cell and gene therapies. We solve complicated problems in healthcare with data-informed commercialization, market access and policy expertise. More specifically, we help our clients navigate the federal and state policy landscape. We also highlight unique value drivers and advocate to critical stakeholders across the healthcare landscape. We aim to be the go-to partner for strategy, health policy updates, data analytics and value economics in cell and gene therapy, which also includes rare and ultra-rare diseases and oncology therapeutics. We do quite a bit of work as well in device and diagnostics.

Paige Nelson:

That’s wonderful. I’m really looking forward to the discussion as we’re gearing up for meeting on the Mesa. At Mix, we’re also excited to work with both pre-commercial and commercial organizations to provide comprehensive talent solutions to support biopharma growth.

Melissa Nocar:

We are kicking things off by discussing drug development and manufacturing for cell and gene therapies with two incredible leaders, Adora Ndu, who is Chief Regulatory Officer at BridgeBio and Susan Nichols, President and CEO of Propel BioSciences.

Paige Nelson:

We hope you enjoy the discussion led by Mix Talent’s Director of Client Solutions and Scientific Partnership, Tori Schaefer.

Tori Schaefer:

Hello everyone and welcome to this special edition of the Mix Tape. My name is Tori Schaefer and I’m the Director of Client Solutions and Scientific Partnerships at Mix Talent. It is my absolute pleasure to be joined by two cell and gene therapy industry experts, Adora Ndu from BridgeBio and Susan Nichols from Propel BioSciences.

Adora has a PharmD and law degree, is the Chief Regulatory and Interim Legal Officer at BridgeBio. She began her career in medical affairs, spent eight years at the FDA and sits on the board of multiple biopharma companies. Adora is deeply committed to advancing safe and effective gene therapies and has a passion for creating opportunities in STEM for underserved minorities. Susan is an experienced biotech executive recently joining the founding team of a stealth technology company focused on the service sector. She holds the title of CEO at Propel BioSciences and provides consulting in the form of strategy, business development, fractional leadership and marketing in cell and gene therapy, drug development tools, technologies and services. As many of you likely know, Susan is very involved in the cell and gene therapy community and is passionate about patient advocacy and bringing innovative therapies to market quickly. Ladies, welcome to the Mix.

Adora Ndu:

Thank you. Thanks for having us.

Susan Nichols:

Thank you so much.

Tori Schaefer:

Well thank you both for joining and helping to shed some light on recent learnings and future opportunities in gene and cell therapy development and manufacturing. Susan I’d like to come to you with the first question. So from your vantage point, what has been one of the most impactful learnings across gene and cell drug development to date in your mind?

Susan Nichols:

It’s no secret from anyone that knows me that I’m a raving CAR T-cell therapy fan. Most recently my son had leukemia and was very distressed that a CAR T was not available when he understood the treatment paradigm. I came into the industry in 2010 and there was just a few patients that we had data on for CAR T therapies and until 2017 the jury was out whether we were really going to have a commercial product. We do. What started in the industry as very manual laborious technique to manufacture cell therapies, going through the process of cryo preservation and then warming it back up for delivery.

This really was the first time this process has ever been done. In 2023, I look back and I’m amazed at how far we’ve come. A lot of these started out as 28 day processes and then they went down the 14-day processes and we were so happy. Now U Penn has it down to two or three days that they have data on and our progress is amazing. These are commercial products that are saving lives and our manufacturing isn’t where it will be ultimately. But it certainly has come a long way.

Tori Schaefer:

Adora, when you think about the biggest changes and you think about speed, as Susan was mentioning with manufacturing, just speeding up that process for CAR T, when you think about speed, is there anything in your mind that has really ramped up on your side of things?

Adora Ndu:

So first I would agree with all that Susan has walked through and I would add that over the years we have seen a pretty significant amount of progress on the regulatory side of things. Granted we still have a long way to go, so I don’t want to state that to suggest by any means that we’re done, things are set, no additional improvement needed. But I do think it’s important to recognize and acknowledge the progress that has been made. So just a few years ago, back in I don’t know 2016, 2017, we had the old framework for regenerative medicine in place and the industry was growing, a number of programs going into the clinic and there was a strong need globally, but particularly in the US to lead that way in establishing the regulatory framework for cell and gene therapies. FDA Sebar moved pretty quickly to roll out a number of guidances to try to start to provide more support even though they were extremely short-staffed.

We externally felt the challenges and the frustrations because as we typically do, we’re moving quickly and things take a long time. Getting clearance for guidances take a long time, authoring those documents takes a long time and so the development was clearly outpacing the regulatory framework. I think we are at a point now, given that over the last number of years FDA has issued lots of clarifications. For the first time we saw Sebar really take a front and center position and PDUFA VII includes many accommodations to help advance the field. The agency led under Peter Mark’s leadership continues to think about how to be nimble, how to be responsive, how to listen to their key stakeholders. So I would say that that’s an area where we have seen a significant amount of progress. There’s more to be done, but I think it’s important to recognize that so that we can continue to build from that.

Tori Schaefer:

Absolutely We’re laying the building blocks and keeping pace with that. So as we think about the FDA and there is this anticipation, a pretty large increase in submissions expected in gene and cell therapy. Can you speak to ways that the FDA is putting different plans in place and how others who aren’t at the FDA can help to support those efforts?

Adora Ndu:

We’re seeing a significant increase as far as developers are concerned. So the Alliance for Regenerative Medicine, ARM, in their more recent report where they contrast the number of developers from 2022 to 2023 and there’s a significant increase just in that development snapshot. So we’re at a point where we have over 2000 developers in the space of cell and gene therapy. Just a need to continue to keep pace with the demand and what we have seen the agency do, more recently, Dr. Marks has announced that they will be rolling out initiatives such as the Operation Warp speed, essentially learning from the pandemic and their ability to really have that open communication and dialogue with developers for the purpose of being responsive, being nimble, and with the goal of getting these products approved quickly for patients.

So they do plan on rolling out a similar initiative for cell and gene therapy, I want to say by the end of this year, if I’m not mistaken. The hope with that is that it creates an opportunity for developers that are advancing products that are promising for patients to have that very close commitment and interaction with FDA via communications, streamlined communications, thinking more about how we can be flexible, how we can apply different approaches to expedite development, whether it be accelerated approval or just thinking about the streamlined clinical development and so on and so forth.

So I would say that’s one of the initiatives that has been rolled out and FDA continues to, Sebar in particular, continues to think about ways to engage their key stakeholders. So whether it be ARM or through having these town halls where they encourage developers to provide questions that could potentially be answered or even the patient-focused sessions that they have held to hear directly from the patient communities, those that are going to be directly impacted by these treatments and those that are living and breathing these conditions. So those are just the few examples of initiatives that Sebar has been advancing, but certainly PDUFA VII includes many provisions that will be important for them, will be important for stakeholders such as ourselves, for companies, for patients. And we will continue to watch those as they unfold and with the hopes of collaborating very closely with FDA as they implement.

Tori Schaefer:

Absolutely. Susan, do you have anything to add on?

Susan Nichols:

I think what really struck me recently is the OTP Super office, learning that it has six divisions and 32 branches, which means that now the reviewers have people to go to for supervision. The workload can be distributed amongst the different branches. And the other thing that struck me is we’re getting there because this is very similar to how the drug development side is currently structured. As far as I’m concerned, I think it’s a huge step forward and it shows the proactive and reactive because we have more coming and we’re still digging out from the backlog of the FDA. We have nine approvals that could potentially happen this year and that’s amazing. It’s the all time high.

Tori Schaefer:

So back to this idea of time. Many of us work for and work with small companies and these delays, whether that be a clinical hold or challenges with manufacturing, they really put the companies at risk. Do you think that this is something that the FDA is thinking about and that reviewers are thinking about? Obviously things are being put in place to move things quickly, but how is that thought of those smaller organizations coming into play?

Adora Ndu:

So I would say that there’s certainly an opportunity for learning and education. There are probably individuals that are thinking about that but not necessarily that it’s their primary thought process. But Dr. Marks has mentioned in some of his sessions that he does think about the small companies that don’t have the time to wait for an extended period of time within the context of a clinical trial, which is one of the reasons he’s a big advocate for accelerated approval. So when we hear leaders like Dr. Marks make those types of statements, at least for myself and I’m sure others in industry, it is reassuring to hear that somebody is thinking about it at the agency. That said, I don’t know that that’s top of mind for the average reviewer. They’re focused on their review work, they’re focused on doing their due diligence, they’re focused on protecting public health and safety, et cetera, which is critical that that is their mission.

There is an opportunity in order to really advance that public health mission. I do think it’s important to think about the big picture as well because if the one company that is developing a gene therapy for a very rare disease that is devastating and life-threatening to patients goes out of business because they have perhaps their program stalled or for other reasons that essentially make it almost impossible to continue with that program. Ultimately we have in that instance also failed the patients. So I think that there’s an opportunity for education, there’s an opportunity for awareness on both sides.

For example, on our end, understanding the challenges that the agency is facing so that we can provide them with what they need, conduct their reviews efficiently and effectively and conversely within the agency, to really understand what their stakeholders are navigating on a regular basis, what it means when feedback is delayed, what it means when meetings are kicked back a month, two months, three months, six months or what it means when FDA tells you, well we need to provide feedback on X before you can move to Y and that feedback takes six to eight months before we receive. Those can be make or break for some companies depending on where they are in their growth and development and what they need in order to advance. But that’s my initial thinking around the average reviewer’s awareness into what companies might need in order to continue their programs.

Susan Nichols:

And I think that that’s where a lot of the Alliance for Regenerative Medicine conversations come in also. There’s a lot of interactions and recently ARM had a potency assay workshop for AAV and 29 FDA representatives attended.

To me that shows that they are in this with us. They want to learn from us, they want to hear where we struggle and what the industry thinking is on ways to improve from where we are. With industry we have the ability to help to educate because we are innovating faster than we can train anyone outside the industry. A lot of what we’re doing is first in man and it’s a twist on a different type of technology. So I think in addition to the FDA coming up to speed as an industry, we need to ask, how can we help?

Tori Schaefer:

You spoke about the FDA is attending these workshops for educational purposes to make sure they understand the advanced technologies and things are developing quicker than many can keep up with at this point. Are there concerns about the labor pool? I know recently with various layoffs and things, there feels to be a little bit of an easing, but I think the expectation is that we will again find ourselves in a place where there is a labor shortage perhaps both on the FDA side but also internally on the company side. What are your thoughts there on how we might work together to overcome some of those issues?

Susan Nichols:

I think Adora was speaking to the August ARM report and it’s pretty heart stopping. We go from 900 drug developers to 2000 plus I believe around 2,700. So think about that from a labor pool perspective. So within a few short years we have just exploded as an industry and we don’t have trained up yet QA, QC, process development, manufacturing. We simply don’t have enough people. So we’re starting to look as an industry and how we help fill this gap because the gap’s only going to get bigger as AI comes in and we’re managing more data. So we have this data management pending and I think that the one thing I heard from one of the ISCT, International Society of Cell Therapy round tables was that there’s not always an awareness of what we do in our industry. So we all sit here and we drink our own Kool-Aid, right? But outside of this industry it falls into that biotech bucket.

So how do we get better at raising awareness in universities and training centers and helping to recruit people into these programs so we can move more into a train the trainer program. We all start to train each other, mentor each other and expand the labor pool. Training’s expensive, it’s not readily available. So all of these factors have to go into planning how we’re going to keep up with the industry, FDA side and industry side.

Adora Ndu:

Yeah, I completely agree. When I think about the pipeline for such a highly technical area, we are not necessarily keeping pace with the growth of the need. Part of it is where’s the pipeline and how can we make that even larger? How can we spread the word and education to those that are coming up through programs that this is an area that they might be interested in. Whether it’s the bench scientists or the physician researchers or pharmacists, all the different fields that are perhaps not quite as aware of this field as they could be. What can we do to create a pipeline through that? Because we’re going to have the needs, we’re going to continue to grow and given how technical this space is, we’re going to get to a point where we don’t necessarily have enough skilled individuals to fill these roles.

On the agency side, under PDUFA VII, they have a significant amount of growth ahead of them and they might feel this in a different way. So it’d be interesting to see how that growth is actionized. I know they’ve been working on filling a number of roles and they have a new director, Dr. Verdun. So She’s also got as part of what she’s going to need to accomplish, which is build this infrastructure for her super office and fill some critical roles and build leaders within that organization. And so it’s going to take some time as new people transition over to OTP, they’re going to need a period of time to get up to speed and we’re going to need to work with them and we’re going to need to continue to educate because there will always be new staff coming on board. So there will be that period of time where we have a critical role to make sure that we continue to engage actively and proactively with Sebar and with the goal of helping them as well because we’re also guilty of recruiting some of their staff.

So we know some really, really great staff that leave the agency and join companies. And so we have to help them as well recognizing that as we pull from the agency, we ultimately collectively will be impacted by that. I know there are a lot of organizations that are thinking about this and thinking about how to help FDA with some of their roles and we’ll just have to work collaboratively because it’s all from the same pool ultimately. Whether that pool goes into the developer side or goes into the regulators side, we’re all pulling from the same source.

Tori Schaefer:

We think about the infrastructure, people, and for gene and cell therapy, CDMOs play a really big role. Are there any concerns with perhaps what could be perceived as a slight lag in gene and cell therapy development that’s making its way to the CDMOs at this point? How are we working to ensure that those CDMOs stay in business and are there when things catch up and manufacturing picks up?

Susan Nichols:

What we could say about that is just some emerging models. Solaris just raised 225 million to take a robotic, basically tool, and build a CDMO around it to increase efficiencies. Is that worth mentioning? Yeah, it is. And the other interesting thing to me is that J&J Legend has this fabulous data on their multiple myeloma drug and had manufacturing constraints. So they knocked on the door of Novartis, who was really the first to commercially figure this out and ask for help. So I think what we’re seeing is a lot of the people who have been there and done that at a commercial scale helping to give patients access across the industry.

Adora Ndu:

And what you’re pointing to is really the key question. How can we be innovative when it comes to manufacturing in order to meet the needs? One example in a much smaller scale where We’re seeing this happen is with the Bespoke Gene Therapy Consortium where under the Accelerating Medicines Partnership, they are working on thinking about how to streamline a number of things including manufacturing, vector production, clinical trials, et cetera. And I think that that’ll be another source for us to learn from with regards to how the consortium is able to bring gene therapy development to the very, very, very, very small conditions in an efficient way. And what aspects of those efficiencies can be translated back to more common or larger rare diseases as well.
Tori Schaefer:

Absolutely. So if we could just for a moment, if we could step back and if either of you could think about those early stage gene therapy companies who are perhaps just starting their journey towards the clinic and commercialization, do you have any advice that you might give to those folks?

Adora Ndu:

So I would say that we have had a number of programs, not that many, but we have had a number of programs approved over the years. The field has seen some success. As Susan mentioned, there are potentially nine approvals this year and that list will continue to grow. So for those companies that are very, very early stage, I think that one important aspect that I would suggest to them is really learning from the past because there’s nothing like precedent in a very quickly evolving field to help potentially avoid making similar mistakes. And that is at every stage, learning from all of those examples and incorporating that in their overall development strategy. Whether it’s on the preclinical, regulatory, commercialization, there are some good examples there. Sounds very cliche, but that’s what I would really suggest, that they take a step back and appreciate and absorb all of those learnings.

Susan Nichols:

And I’d add, develop the community, because a lot of those learnings are passed on just because we end up randomly falling into a conversation and then we have a need and remember, oh, I was at Bio and in this group of people and so-and-so mentioned this and now I need that, I’m going to call and get a referral. A lot of this has been done and getting the people on board who have done it before is instrumental. I find that in this industry, it’s a great peer community who generally wants to help everyone because we come into this and these are new therapies, it’s not easy and we know the path that you take.

And looking back, I think the majority of people in this industry turn around with a handout saying, how can I help you avoid where we fell and how can I help you learn from the successes we had so that we don’t keep reinventing the wheel, so that we stand on the shoulders of the giants before us. I think the other learning is how much value our patient community can bring, all the way across from the very beginning to understanding the patient journey, understanding the route of administration, what good endpoints are from a patient perspective, not just a regulatory perspective and getting to know not just the disease but the people who have that disease. The patients will help any way they can. They just need to know how and helping them come on the journey with you helps you both.

Adora Ndu:

I couldn’t agree more with that, Susan. Really critical.

Tori Schaefer:

Well thank you both for that. So as we start to close out this episode of the podcast, is there any topics that we didn’t cover that you think might be important for our audience to hear?

Susan Nichols:

I think it’s important for the audience to hear that the market’s showing signs of recovery. Specifically in our sector in the last couple of months, we’ve had a couple IPOs, there’s five to 10 more expected in biotech as an umbrella by the end of the year. Venture capital firms are refueling such as Westlake, they put another 450 million in big pharma. Vertex put another 200 million in their fund. AstraZeneca picked up the rare disease assets from Pfizer. From my perspective, we’re starting to see the tides turn in our favor.

Adora Ndu:
I think you said it all Susan. It’s exciting to see that tide starting to turn.

Tori Schaefer:
So ladies, no Mix Tape would be complete without me asking each of you two additional questions. The first is, what is your favorite interview question? This can be something that was asked of you or perhaps a question that you’ve asked others as well as what is your favorite song so that we can add that to our Mix list for you. Adora, I’d love to start with you.

Adora Ndu:
This was probably the hardest set of questions out of all of the discussion questions that you shared. I wouldn’t say this is my favorite interview question, but I would say this was the most interesting interview question that I have heard in all my years, which is if you were an animal, what would it be and why? I actually received that question in one of my early FDA interviews when I was still very early in my career in transitioning to the agency and I thought it was interesting.

And as I went through to answer that question, I could see why they would want to understand just sort of what your state of mind is, what type of animal do you connect with and what are the reasons. It’s just a way of thinking and processing things. So I thought that was interesting. As far as my favorite, is it favorite artist, favorite song? I actually asked my husband to help me with this one. He said, you don’t have a favorite. You go in seasons. So I think that’s right. I sort of find something and I play it over and over again for several months and then I move on. But the one artist I always come back to is an artist by the name of Maxwell and one of my favorite songs that he composed is called, This Woman’s Work.

Tori Schaefer:

I’m very much like you with the seasons of favorite songs. So I can very much appreciate that. So thank you. Susan, favorite interview question and song.

Susan Nichols:

So my favorite interview question I like to ask because most of the time I’m hiring BD related people, is tell me about a time when you wanted a role so much that you were unstoppable until you got it?

Tori Schaefer:

I like it. I like it. Do you recall perhaps your favorite answer?

Susan Nichols:

I had an interviewee look at me once and say, how do you think I got here in front of you?

Tori Schaefer:

Okay. Okay. Did you hire that person?

Susan Nichols:

I did. I did actually.

Adora Ndu:

There you go.

Susan Nichols:

He did some work, some very creative work, that was exactly the person we needed in that specific BD role.

Adora Ndu:

I like that question. Yeah, very appropriate.

Tori Schaefer:

Absolutely.

Susan Nichols:

And my favorites… See, this is hard for me because I have themes. So if I’m doing a pitch, it is always putting Confident on by Demi Lovato. If I’m celebrating, my sisters and I always celebrate together on the phone dancing to Cake By the Ocean, because how can you listen to Cake By the Ocean and not dance?

Tori Schaefer:

Well ladies, thanks again so much for joining us on this version of the Mix Tape. Some of the biggest lessons that we’ve learned today are learn from the past, become part of the solution, value the patient community. And last but certainly not least, things are looking up for gene and cell therapy from all corners of the business. So again, thank you for joining and I hope you have a lovely rest of your day.

Adora Ndu:

Thank you Tori.

Susan Nichols:

Thank you Tori so much.

Melissa Nocar:

Thank you to Adora, Susan and Tori for an insightful discussion. I especially enjoyed the attention to detail that each of our guests brought to the discussion surrounding challenges and opportunities in preparation for commercialization as we look ahead. Such pearls of wisdom.

Paige Nelson:

Agreed, I really enjoyed the discussion regarding early and proactive communication with the FDA. The lasting impact of working complimentary with the agency is a paramount takeaway.

Melissa Nocar:

Couldn’t agree more. With the rapidly evolving landscape, education and collaboration is beyond important. Be sure to join us for part two where our guests will discuss the cell and gene therapy approval and post-approval process in the journey to commercialization. Thanks for being in

Paige Nelson:

Thanks for being in The Mix. We’ll see you next time.