April 27, 2018
“We're really pushing the boundaries looking for non-addictive pain medications and looking for ways to achieve that. Then on top of that, we’ve developed new ways to look at immuno-oncology and immunotherapy. Obviously this is an area that's really at the forefront of science right now and in the news. It is exciting to be carving out a new area that's been largely unexplored.”
Dan Goldberg
Director of Discovery Research at Kineta, Inc.
Dan Goldberg has twenty years of drug discovery industry experience enabling research strategies from target selection to IND candidate. He has led the advanced four clinical development compounds from early drug discovery through regulatory toxicology, and has successfully completed single and multi-ascending dose portion Phase 1a and Ph1b clinical trials for most recently developed asset KAR5585; Phase 2 studies will commence circa 3Q17 as a once-a-day treatment in patients with PAH. Dan is passionate about drug discovery and open communication and strongly motivated to get drug candidates into the clinic.
Interview by Barry Bunin and Isaiah Hankel from CDD, April, 2018.
Barry Bunin:
Hello. This is Barry Bunin. I'm here with Dan Goldberg and Isaiah Hankel to do the next CDD spotlight. If you could introduce yourself Dan and I'll hand it to Isaiah for the rest of the questions. That would be great.
Dan Goldberg:
Sure thing Barry. This is Dan Goldberg. I'm the director of MedChem and Discovery Research here at Kineta in Seattle, Washington.
Isaiah Hankel:
Hi Dan. Great to have you on. I'd like to start with a general question. Maybe you could tell me a little bit about your research and what you do at Kineta.
Dan Goldberg:
We have a broad portfolio, but are focused primarily in two main therapeutic areas; chronic pain and immune-oncology. It's been a very exciting time, being at the forefront of both of these very important areas of research. We also have projects that cover neuroscience and biodefense as well. We have a lot of core expertise internally, but where there are gaps, for example with Chemistry, we collaborate with external resources.
Isaiah Hankel:
Great thank you. Can I ask you what the end goal is or overall strategy of Kineta is? I'm curious, what is it that gets you up into Kineta every day and gets you working? What are you excited about?
Dan Goldberg:
For me the fundamental goal is trying to discover a new beneficial therapy for patients and having the opportunity to come in and work with a vibrant group of individuals who are excited to do cutting edge research and really look for new therapies and new medicines. To be part of that team is what makes it really exciting for me and what drives me to think about the next goals and objectives both personally and professionally within the organization.
Isaiah Hankel:
Great. What would you say has been the biggest win for Kineta so far? Something that you're most proud of within the company.
Dan Goldberg:
I think it's a combination of factors. I think we're really pushing the boundaries looking for non-addictive pain medications and looking for ways to achieve that. Then on top of that, we’ve developed new ways to look at immuno-oncology and immunotherapy. Obviously this is an area that's really at the forefront of science right now and in the news. It is exciting to be carving out a new area that's been largely unexplored. This is something that has really pushed the boundaries for us here internally.
Isaiah Hankel:
That's great. I actually have a spinoff question about. I'm curious, just outside of your research at Kineta, because you mentioned the field of immunotherapy. What's one of the most fascinating developments you've seen overall in the field of immunotherapy?
Dan Goldberg:
I think it's really just better understanding how the body can modulate the immune system. Obviously there have been great strides but there are clearly some deficits associated with immuno-oncology. It's not [yet] the panacea that I think we all hope for. I think we are improving our handle on safety and tolerability. I think it's still in its early days, but I believe we’re going to be part of improving upon what's already out there in terms of useful medicines.
Isaiah Hankel:
Great. What is it that you're delivering to patients or working on overall? What’s the biggest outcome that you're close to achieving or that you want to achieve?
Dan Goldberg:
We have a couple different things. We have a program focusing on arenaviruses including Lassa fever. As well, we are working on a non-opioid for the treatment of chronic pain. Additionally, we are working in the field of rare diseases and vaccine adjuvants.
Isaiah Hankel:
And you mentioned balancing internal versus external resources. Can you talk a little bit more about that?
Dan Goldberg:
We have an opportunity here where we have 35 internal employees. We have a vivarium as well so most of the Biology, the analytical support, we can do internally. As we think about more broad reaching areas, in terms of Chemistry, we externalize that both nationally and internationally. We really look for the best fit of purpose depending on what we need at the time. I think what's nice is we have a lot of experience internally that allows us to choose the best external partnerships and it's always a balance. What can we do in internally versus what can we need to externalize?
Isaiah Hankel:
Absolutely. I'm curious; you mentioned the importance of your team. Can you talk a little bit about your team? What makes them so special and what kind of collaborative environment have you structured.
Dan Goldberg:
The team comes from a combination of both academia and biotech experience. We're able to capitalize on our network and connections to really identify the best opportunities, with the best science that we can do for the current projects. Each of the programs has a small team but there's a lot of crosstalk and functionality amongst them. There is a continuous dialogue to move the projects in a smooth and efficient manner.
Isaiah Hankel:
You obviously have experience in academia and beyond. I'm curious about your formative experiences at both Emory and the University of Chicago?
Dan Goldberg:
I received my PhD at Emory University and that was an interesting time for me because I worked for an assistant professor. I was his first student that graduated with a PhD, and it required me to be creative in a setting that didn't have a lot of funding to begin with, as most assistant professors do not. It felt a lot like a biotech in some ways because we did not have the infrastructure or resources that say more established labs had. Again, we had to be creative in terms of how we moved the projects forward, and it enabled me to build on my cross-functional teamwork and communication skills to really get things done. I always subscribe to the philosophy of beg for forgiveness versus ask for permission, and I think in that environment you have to really be driven to accomplish something when you don't have a lot to start with.
Then moving to the University of Chicago for my post-doc, which was in a well-established lab. I spent a lot of time teaching graduate students and undergrads so, it helped to teach me ways to build and harness teams, which has been beneficial in my career. After I left the University of Chicago I went to work for Boehringer Ingelheim Pharmaceuticals for over 13 years, again a very well established organization. For me it was where I wanted to start my career because I knew nothing about drug discovery, and I wanted to be in an environment where I could really grow, and develop, and learn the entire [drug discovery] process from hit stage to clinical development.
That really set me up for moving into the biotech world where after Boehringer where I went to work with Karos Pharmaceuticals, which was a true start up, composed of only nine individuals. There within the span for five years we went from an idea on a piece of paper to a clinical phase two asset. Here it taught me how to do drug discovery in a nontraditional manner, unlike a large pharmaceutical company. That was an incredible experience. Having to establish a broad network and building all the different teams externally because with nine people you really have to lean on external partnerships.
After that I decided to move over to Kineta, which being larger and had an established infrastructure, but not too big, and allowed me to build upon all the lessons I've learned over the past 18 years at that point.
Isaiah Hankel:
That's an impressive career experience. I am curious to hear more about the differences between working for these pharmaceutical companies, large or small, versus working for Kineta right now. What would you say are some of the key differences or similarities?
Dan Goldberg:
I think the biggest difference in working in a large company is you can walk down the hall and talk with anyone in any discipline. You don't have to think about what you don't have. I think the other aspect is that if your current project fails there's a pipeline of projects to work on. I think in the smaller companies, failure is not an option. You don't have this density of project after project because you don't have the people to be able to manage that many projects at the same time, nor do you have every single discipline lead that you may desire or have in a large company. You have to wear a lot of hats, so to speak. You have to be able to network efficiently, and you have to be able to figure out what you know, and what you don't know, and then with the things you don't know, where can you get them in the most reasonable and cost effective manner.
Isaiah Hankel:
Perfect. I think Barry had some questions too. Barry do you want to jump in?
Barry Bunin:
Yeah a little bit. So we have some interesting parallels. I grew up in the suburbs of Seattle, was just there last week and I was actually Jonathan Ellman’s first grad student at Berkeley, so I remember what it's like setting up a new research group and working at smaller companies and larger companies in drug discovery. I guess my questions are around how you came to evaluate CDD Vault, why you chose this technology, and how it's been helpful for you at Kineta?
Dan Goldberg:
The way I came in touch with CDD, Barry, is that before I left Karos we had hired some external chemists that would shepherd the program after my departure and as it moved from an early to a later stage clinical asset. Both of those chemistry consultants had worked with CDD in the past and before I had left they introduced me to CDD Vault, and I understood the functionality associated with that. With a large company you have a number of different infrastructure resources and database management, both homegrown and not. Looking at what the capabilities were with CDD Vault and then how you could integrate that across an organization was very attractive to me, and so I took that knowledge that I had gleamed in the short time I was left at Karos and brought that over to Kineta.
I find it to be an incredible useful tool. The team members here are using it on a daily basis. It allows us to harmonize and harness all the information that we need in one central location and it's really very intuitive and very user friendly.
Barry Bunin:
What would you say are the top two or three areas of functionality that you guys use the most or like the most in CDD Vault? It's always developing new capabilities.
Dan Goldberg:
I think a lot of it is structure or substructure searching. Property calculations. Then obviously going through the data is quite helpful. Then being able to export different files is also very useful.
Barry Bunin:
On the other side. Are there any either new capabilities which were recently rolled out or that you would like to see us roll out in the future?
Dan Goldberg:
I think the thing that's always an interesting one for me and it all depends on ability, how do you graphically view data. It’s easy to see numbers but they become blurry over time in any program. I think having ways to graphically visualize information in different ways is always very helpful.
Barry Bunin:
Moving from the technical questions to more the people questions. Could you share some memorable interaction with you've had with another brilliant scientist? It could be from your time as a postdoc, or at Boehringer Ingelheim or more recently that you could share with us.
Dan Goldberg:
I had a very unique opportunity when I was at the University of Chicago to host Bob Grubbs as a seminar speaker, long before he co-won the Nobel Prize in Chemistry with Yves Chauvin and Richard Schrock (https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2005/). I had worked with the Grubbs catalyst as part of my PhD work in developing new carbene chemistry that gave me a hands on understanding of the chemistry and what it was like to make these type of catalysts. So it was great to meet the father of this chemistry and to see how personable he was. Having a chance to listen to him in terms of his insight, in terms of research, have more of a social endeavor with him, going out to dinner. It really stuck with me as it was someone who I looked up to, and to finally meet this individual on a personal level and then to think about how their research had really changed the paradigm of chemistry was really a phenomenal opportunity for me and something I still reflect fondly upon.
I think you're constantly having important interactions, even beyond the meetings with famous scientists. I'm constantly interacting with people who make me think differently on a day-to-day basis in any organization. I believe you can learn from anyone and I think you have to have that flexible of thought to understand what people bring to the table. I really try and look at that carefully with all the team members and all the people that I work with, both internally and externally because they've helped me grow as a scientist just through constant feedback, and communication, and teaching.
Barry Bunin:
One of the interesting things about the Grubbs metathesis catalyst is they can make carbon-carbon bonds and I believe it can do so in water and sometimes in the presence of biological systems as well. I'm curious if you use that technology either in your academic or industry research.
Dan Goldberg:
No. I didn't. For me a lot of my work was with all the Schrock carbene chemistry. I didn't have the opportunity to do that work in the aqueous environment, but I made some modifications to the Grubbs catalyst internally. Nothing that was as seminal as the work that many others have done, but it really helped me appreciate the fluidity and versatility of those systems. I think when I was early on looking at these high oxidation Schrock carbene, they couldn't be done in the presence of much and now, as you said Barry, you can do it in the presence of almost anything. It really highlights the potential and really how this chemistry has changed in the past 25 years.
Barry Bunin:
Moving from the interesting academic research to the applied industrial research. Can you talk about some of the drug discovery projects that you've failed to take in to the clinic and what have been successful, that you've learned from those, but also some of the projects that didn't get in to the clinic and what you learned from those as well, so we get a sense of the scope of your experience as an industry without having to do them ourselves.
Dan Goldberg:
The most recent project, the TPH1 project, or the tryptophan hydroxylase 1 project (https://en.wikipedia.org/wiki/TPH1), for pulmonary arterial hypertension is ready to go into phase two clinical trials and that's the work from Karos. For me it was really the repositioning. We had initially started that project looking at a completely different indication and needed to pivot midstream based on data that we were obtaining on the initial indication. At least the data that's been published out there publicly now, we are seeing a strong reduction of serotonin and it was really nice to see that we could modify this peripheral endocrine hormone, serotonin, and do it with a small molecule. That to me was really exciting.
The project there was a very different one in terms of the properties of the molecules required and the complexities of tissue distribution. It was, again, predominantly based on structure based drug design. I've spent a lot of my career using structure based drug design especially in the field of kinases. Those tended to be, unfortunately, ones that weren't as successful, although I think chemistry wise we could make drug-like molecules, we could get very potent molecules, but I think at the time our understanding of on versus off targets selectivity wasn't as granular as it is now; and unfortunately, I think the pendulum had swung back and forth within industry of the favorability or un-favorability of finding drugs in kinases. I think the needle has moved back again now to the move favorable side, because we're seeing a lot more research to continue in the kinase world and we're now seeing exciting therapies like the JAK inhibitor from Pfizer that are emerging. I still really enjoy thinking about kinases and I'm curious to see how the field continues to progress since I was not as successful from a clinical perspective.
Barry Bunin:
One of the things we have in CDD public is the PKIS kinase data from GSK and ChEMBL Kinase SARfari data as well as the GPCR gene family wide data from Bryan Roth’s PDSP Database and a hundred other public data sets that people can look at together with their SAR and imagine some of these might even be useful in the immuno-oncology field for potential combination therapies.
Dan Goldberg:
Probably, yeah. That's good information to know, something to look into a little bit further.
Barry Bunin:
Last couple questions from me. Can you share, in addition to the technology, some of your interactions with CDD as an organization and the people for getting you set up and getting you to steady state efficiency with CDD vault technologies?
Dan Goldberg:
Absolutely. It's been a great experience. Everyone that I've dealt with, from Sylvia, from the business angle, to the technical service experts like Charlie and the technical staff has been very smooth and easy to work with. Any time there's a question that comes up there's been quick response. There has been diligence both either through GoToMeeting or on the phone. It's just a very hands on organization. It’s a very passionate group of people to really help drive the drug discovery process and to make CDD both successful internally and for your clients. I look at it as a very strong collaboration and very positive interaction.
Barry Bunin:
One last technical question on my side. You'd mentioned the immune-oncology area that we're learning more all the time, and it's in its infancy. As the infant starts to crawl, and walk, and talk, what do you see as some of the interesting developments that either have occurred recently or that you have an inkling are right around the corner since you are familiar with and you are working in that field. There's been a lot in the general public media about that field but just on the scientific side working in the evolving field, what have been some of the interesting developments?
Dan Goldberg:
I think for me it's what the best targets to drug are. What are those that could be great for combination therapy? Again, looking to increase safety and tolerability is still something that we understand and I think that's where things are going to be driving towards in the near future, and I think that understanding is going to be very beneficial both for patients and for scientists that are investigating in this area. That's what I see as sort of the big things that are coming forward in the next short while.
Barry Bunin:
That's it for my side. If you guys have other questions or comments for any of us, it really was great to hear about your industry experience as well as your anecdote from your meeting with Bob Grubbs.
Isaiah Hankel:
I have two more questions if it's okay.
Barry Bunin:
Sure.
Dan Goldberg:
Yeah sure Isaiah. No problem.
Isaiah Hankel:
If you were giving advice to future PhD's who want to get into a field similar as yours, whether they wanted to get into working with pharmaceutical industry or large or small company, doing your work, if you're speaking to a future chemist or a pharmacologist. What might that advice be or what comes to your head when I ask that question?
Dan Goldberg:
It's actually a great question because I talk to my kids about this a lot. When I started my college career, I was tracked to go in to medical school and even to this day I sometimes wonder should I have gone more into medicine versus research. What I did not fully appreciate at the time was the number of opportunities that there are for a PhD scientist. We think about going into the pharmaceutical industry or academia but I think in hindsight there are so many different opportunities from the venture capital world, to the patent world, to the business development world. I think in having a really strong PhD gives you an opportunity to think about how to ask the hard questions and think about things holistically and so I would broaden your perspectives and what I recommend to early scientists is broaden your options out there. While you may be passionate today about working in biotech, there's a lot more out there. I think having that opportunity to think about your career more globally and more than just one dimensional is really important.
That's the advice I wish I was given. I tracked early on into a career into the biomedical sciences and basically stayed. In hindsight I think there were other avenues that could have been explored. I think it's something to consider for creative individuals and people who are driven, there is a lot out there to do beyond your traditional path to senior scientist, and then, say, to a CSO of a company, although that's a great opportunity, I just think there's more out there than at first blush.
Barry Bunin:
That's a great note to end it on. An inspiration for our children. Thank you Dan, this was a great spotlight interview and we'll look forward to talking with you in the future.
This blog is authored by members of the CDD Vault community. CDD Vault is a hosted drug discovery informatics platform that securely manages both private and external biological and chemical data. It provides core functionality including chemical registration, structure activity relationship, chemical inventory, and electronic lab notebook capabilities.