The First-Time CEO Using a New Paradigm to Attack Metastatic Cancer
Does an IO therapy have to go after cancer cells to get rid of cancer? Noor Jailkhani, PhD, CEO and Co-Founder of Matrisome Bio, argues that targeting the extracellular matrix, usually seen as a barrier, could be a boon for treating hard-to-treat and metastatic disease. Dr Jailkhani discusses her technology, her vision and her experience as a first-time CEO.
Most therapies target the cancer cells themselves. Why are you focused on the extracellular matrix?
Despite their promising success, therapies that target cancer cells alone have several limitations, largely attributed to the heterogeneous nature of cancer cells. Even today, most cancer related deaths are due to metastases, highlighting a huge unmet need to find new ways to target metastatic cancer. The extracellular matrix forms a major part of the tumor microenvironment, and the matrix of disease tissues is very different from the matrix of normal tissues. We're interested in the matrix because while cancer cells are very heterogeneous and mutable, components of the disease matrix are relatively stable. Additionally, some of the targets that we're going after in the matrix are shared across tumor types, which means they are cancer-agnostic. That means that therapies against these targets can be used across cancer types, across patients and in cancers that metastasize to various sites.
There are many metastatic solid tumors and metastases that don’t respond to cancer cell-targeted therapies or current immuno-oncology therapies. Our entire focus is to move away from targeting cancer cells to targeting the extracellular matrix, delivering therapies specifically to the disease matrix surrounding tumors and metastases.
What is the matrisome?
The matrisome refers collectively to all the proteins present in the extracellular matrix, which is a meshwork of proteins that surrounds every cell in the body, including diseased tissues like tumors and fibrosis. Therefore, it is a big part of the cancer microenvironment.
The matrix of diseased tissue is very different from the matrix of normal tissue. We have spent decades identifying what these proteins are, which play both biomechanical and biochemical roles in disease progression.
"Our entire focus is to move away from targeting cancer cells to targeting the extracellular matrix, delivering therapies specifically to the disease matrix surrounding tumors and metastases."
What does this approach address that current therapies can’t?
Our platform and approach are cancer-agnostic and can potentially be used across solid tumor indications. We are particularly excited about the potential impact on metastatic disease. Currently, cancer cell-targeted therapies have limited efficacy against metastatic disease. Metastasis is estimated to be responsible for approximately 90% of cancer-related deaths. Unfortunately, Stage IV metastatic disease often carries a grim prognosis for patients. The targets we are focusing on are widely expressed across various metastatic sites and patients.
Why hasn’t the matrisome been leveraged for therapies until now?
For several technical reasons, the matrix has proven challenging to study and characterize. Additionally, the matrix remains underappreciated and is often overlooked as a potential translational or drug target. We spun out of the Hynes Lab at MIT, a pioneering force in matrix biology for over five decades.
In the past decade, significant technical advancements, particularly in ECM enrichment methods and proteomic approaches, have facilitated the characterization of the "Matrisome”. This progress extends to the analysis of patient samples, including tumors and metastases. At Matrisome Bio, we have reached a pivotal stage where we are transforming this Matrisome into a therapeutic opportunity.
Compared to cancer cells, how much bigger is the extracellular matrix as a target for therapies?
All solid tumors and metastases have extracellular matrices. In fact, in some very aggressive tumors like pancreatic cancer, 30-90% of the entire tumor mass may be extracellular matrix. The matrix therefore represents a huge, but under-explored, therapeutic opportunity.
At Matrisome Bio, we are converting this meshwork of proteins, which has largely been viewed as a barrier, into a drug depot. Our platform is based on protein binders carrying different therapeutic payloads to the tumor matrix. When injected into cancer patients they would circulate in the body and bind specifically to the diseased tumor matrix, thereby delivering a variety of cytotoxic and immunomodulatory agents to bring about anti-tumor effects.
How does delivering it to the matrix impact the actual tumor cell?
The tumor cells are closely attached to the extracellular matrix. For the purpose of tumor immunomodulation, you are actually activating immune cells in the tumor microenvironment and internalization of immunomodulatory agents like cytokines is not required. There is data on the efficacy of tumor matrix targeted cytokines.
This is also what we have seen with CAR T-cells. We collaborated to show for the first time that matrix-targeted CAR T-cells, which were based on our binders, were effective in murine melanoma models. When these CAR T’s bind to the tumor matrix, they recruit endogenous immune cells to elicit anti-tumor immunity.
"If successful, this endeavor could pave the way for off-the-shelf solutions that might eliminate the need for patient type-specific or cancer type-specific therapies."
What is possible next if your technology is successful?
If successful, this endeavor could pave the way for off-the-shelf solutions that might eliminate the need for patient type-specific or cancer type-specific therapies. The matrix targets we are pursuing exhibit cancer-agnostic properties, being expressed across various solid tumor indications and in different metastatic sites. The potential lies in the universality of the therapy, capable of addressing both solid tumors and metastases irrespective of their origins. Should this technology prove effective, its ramifications could be monumental across all these domains and importantly for metastatic disease.
What advice were you given about making the transition from scientist to CEO?
What I learned the most was that you have to network, and you have to make the most of every resource you have. I reached out to my network of friends and extended family, as well as folks who'd been in startups. I met a lot of investors as well. With every interaction, I learned something that I took back into my work. I took every piece of advice from them. This was a big idea. I learned how to think about a specific business plan, how to think about a budget, how to assemble the right kind of team.
What have you learned specifically being a first-time CEO?
Being a first-time CEO has been an enlightening and exciting journey and has required a delicate balance of learning, vision, and action. Embracing a growth mindset, staying true to our vision, building a stellar team, seeking wise counsel, and trusting intuition have been integral to my journey thus far.
"Successful pitches hinge on honing your vision, seeking feedback, and passionately conveying your conviction to investors. By doing so, you can forge partnerships that drive your venture forward."
What made you successful in pitching to investors?
Successful pitches hinge on honing your vision, seeking feedback, and passionately conveying your conviction to investors. By doing so, you can forge partnerships that drive your venture forward. In my experience, seeking feedback from seasoned investors and bio-entrepreneurs was pivotal. Their insights helped refine broad ideas into specific, actionable plans. As a founder and CEO, it's essential to deeply understand your company's vision, technology, and potential pitfalls. This clarity enabled us to passionately convey our vision to investors.
Investors seek conviction and passion in a founder's vision. Articulating this vision effectively to investors is paramount. It is not merely about presenting a set of slides or financial projections; rather, it is about sharing a compelling narrative that ignites conviction and enthusiasm in potential partners. Investors need to see your unwavering confidence and passion in the vision you are presenting. They need to believe in the potential of your technology and its ability to make a meaningful impact.
What are the specific modalities or pathways that you’re keeping an eye on?
One area that truly excites me is the tumor microenvironment. I firmly believe that further exploration and understanding of its composition and dynamics concerning disease progression and treatment will significantly enhance our ability to combat tumor immunosuppression and enhance the longevity of therapy responses.
What is your career advice, especially for young women who are entering science careers?
Connect with mentors, follow your passions, stay curious, and keep that growth mindset alive. Your journey is uniquely yours. Build your network: connecting with mentors and peers can be a game-changer. For me, reaching out to people outside my immediate circle opened my eyes to a world of possibilities in life sciences.
Finding your passion and purpose is like finding your North Star in science. It's what keeps you going, even when things get tough. I've found that when I'm truly passionate about what I'm doing, it doesn't feel like work at all – it feels like a calling.
Maintaining curiosity and adopting a growth mindset are essential. These qualities foster resilience and adaptability, enabling us to embrace new opportunities. With a growth mindset, you're not afraid of failure because you see it as an opportunity to learn and improve.
Book Recommendations:
The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee & Venture Deals by Brad Feld and Jason Mendelson. This is a great book for first time founders/entrepreneurs who are starting their fundraising and company creation journey.
