Recently, we had the opportunity to speak with Robin Mansukhani, the founder and CEO of Deciduous Therapeutics, a San Francisco-based biotechnology company focused on restoring immune function to combat diseases of aging. Deciduous Therapeutics is pioneering the use of the body’s own immune system to target and eliminate senescent cells—damaged cells that accumulate over time and contribute to a wide range of age-related diseases, including fibrosis, metabolic disorders, and more. With a strong focus on leveraging Natural Killer T (NKT) cells to clear these harmful cells, Deciduous is developing novel therapies that could potentially transform the treatment of conditions such as lung fibrosis, autoimmune diseases, and even age-related macular degeneration.
In this interview, Robin Mansukhani shared insights into the company's groundbreaking research, its current progress in drug development, and the challenges and rewards of building a biotech startup from the ground up. We also discuss the broader future of anti-senescence therapeutics and Robin Mansukhani's advice for aspiring entrepreneurs in the biotech field.
Could you describe your company, and the problem that Deciduous Therapeutics is trying to address?
We are a company based in San Francisco, California, and we were founded with the mission to restore immune function as relates to diseases of aging. Within that, our primary focus is on removing senescent cells. Senescent cells are these highly inflammatory deleterious cells that accumulate in the presence of disease and also as we age normally. The good news is that the immune system can normally recognize the senescent cells and remove them quite effectively. However, as we age and with disease, the immune function that would normally remove these cells becomes compromised, which leads to the development and progression of a number of age related diseases. Therefore, therapeutically, what we are doing is restoring the immune system's ability to remove these deleterious pathological senescent cells. The uniqueness here is around restoring the immune systems ability to do what it was intended to do. And that may not sound like a revolutionary idea, but obviously how you do it, which part of the immune system you target, and doing it safely are the key parts of the discovery.
What makes your product unique in this field?
The value proposition is that we can understand the immune system and specifically target a very small portion of immune cells called natural killer T (NKT) cells which have the endogenous ability to kill pathological senescent cells. Before our company came along, it was believed that the immune system could naturally ablate senescent cells but it was not clear how and which immune cell specifically could do this. We determined which immune cell population removes senescent cells and designed novel drugs that can restore their function. Most importantly, restoration of NKT cell function and removal of senescent cells results in the resolution of both metabolic and fibrotic diseases.
Where is Deciduous Therapeutics currently in your drug development scheme?
We've identified a suite of lead compounds and run safety and efficacy studies on them. They look both efficacious and clean from a safety profile. We are now in the process of scaling up the production of these compounds, so we can run larger scale studies on larger animals to prepare for filing an Investigational New Drug Application with the FDA.
What potential diseases do you guys think you could treat or with your compounds?
There's a suite of diseases that we've already shown that we can treat pre-clinically and there's a suite of diseases that we could potentially treat, but haven’t produced data for yet. There are maybe 20 to 25 indications that are driven by senescent cell accumulation. It can be anything from metabolic disease, various fibrotic diseases, autoimmune diseases, brain disorders, frailty, sarcopenia, kidney disorders, liver disorders, heart disorders, and even type one diabetes and Age-related Macular Degeneration. There are a lot of indications we can go after, but right now we are focusing on lung fibrosis and metabolic disease.
What are the future goals of Deciduous Therapeutics?
Our goal is to help a number of patients who are suffering from these diseases caused by the excessive accumulation of senescent cells, with lung fibrosis being one of the most catastrophic and difficult to watch. The survivability is quite, quite low and currently patients do not have effective treatments available to them. That's the goal: can we improve the lives of patients?
Where do you see the field of anti-senescent cell therapeutics going in the next 5 or 10 years?
I think it's going to be a very important therapy. For some indications, it'll be a combo therapy provided with the current standard of care for that specific indication. For others, given what's out there right now, it'll be a monotherapy. Anti-senescence approaches are going to impact skin disorders, fibrosis, and certainly metabolic disease. Down the road, I think they will play a role in treating additional indications such as neurological disorders, frailty, and sarcopenia, which are really core to the aging process and diseases driven by the accumulation of senescence cells.
Do you think there are any areas within pharmaceutical development and biotechnology that are not being pursued or are under-pursued that you think there should be more emphasis on?
I think there are certain indications where the current standard of care is generally effective both from a treatment and cost standpoint. As a result, what would you have to show to beat that standard of care is discouraging for companies to even try. However, cardiovascular disease is the number one killer in the United States and I view this area as an under-explored opportunity, especially given it’s causal link from Type 2 Diabetes or Metabolic Syndrome.
Switching gears a little bit, as a startup founder, how do you foster a culture of innovation at Deciduous Therapeutics?
One thing we try to do here is make sure everyone has a voice no matter your position within the company. It doesn't matter how long you've been here or your background. Everyone gets a voice to put forth ideas and they'll be taken seriously. I think great ideas can come from everywhere. On great teams, everyone is a role player. We're all stars in different ways at different times. No one is seen as more important than the next person.
What are some of the biggest challenges you guys have faced?
I think identifying the target initially was always a challenge and finding the right molecule to restore the NKT function was initially challenging. Beyond that there have been a lot of translational challenges. That is, building a package to support that in vivo preclinical data actually matches up well with the human condition and demonstrating that convincingly before going into human subjects. Putting all those pieces together and having them go in parallel well, is challenging, but really, really important.
Looking back at your time at Case Western Reserve University, is there anything that's impacted you in your career?
Yeah, the work ethic. Case Western Reserve University is tough. There's a lot of work and there were no excuses made when work didn't get done. That kind of hardens you and it teaches you how to rise up to what's needed to succeed. It wasn't easy, but that's okay. I think that was the point. I think at the end of the day, once you rose up to the challenge there was a great sense of satisfaction to be pushed to work to your limit and come out of it okay. So, you know, it's a little bit of pain for a lot of gain later.
Do you have any lessons you want to share from your career journey?
The time is always now. I think if you want to do something, you have to jump in and try it. I think most people are typically quite risk averse and they want to run towards security. If you're a person that can run away from security and run into things that are more challenging and more entrepreneurial, it won't be crowded. I can promise you that. Most people are going to want the obvious kind of stable and secure life and I think that's great for most people. For those who have that itch to be an entrepreneur, just know it's going to be lonely, but once you get into it, you may never want to go back. What you can achieve from starting your own companies and building your own products and ideas from scratch is really satisfying. You're going to give up some security, but the end goal and the end prize will be substantially bigger if you get there. It just depends on how you want to live your life.
Do you have any advice for any aspiring entrepreneurs?
Get in and try really hard. Make a lot of mistakes. Talk to a lot of people. Be a brilliant networker and make a lot of friends. Most people are going to tell you it's not going to work, but you have to decide that for yourself. Most people are going to say it won’t work because they can't fathom doing it themselves, but you have to know differently. When it gets tough, try that much harder and eventually you'll get there. It won't be easy, but that's the point. That's why you're doing it and not other people.
Deciduous Therapeutics is one of the CWRU-founded ventures in the CWRU Alumni Venture Fund portfolio.
This article was written by CWRU Alumni Venture Fund Fellow Brendan Sheehan, MD-PhD class of 2030.