Two Harvard Biotech Entrepreneurs Are Creating The “Trojan Horse” Of Cancer Treatment
Existing methods of cancer treatment are expensive, risky, and carry adverse side effects for patients. Two Harvard researchers turned entrepreneurs are engineering drug therapies to increase the effectiveness of available treatments and decrease cancer patients’ emotional, physical, and financial burdens.
Nathaniel Brooks Horwitz and Nikita Shah founded Nivien Therapeutics to create the next generation of cancer treatments to augment current approaches. They share a common goal of increasing the effectiveness of chemotherapy and other standard treatment options and improving the patients’ quality of care.
Yet, their approach is radically different from incumbent pharmaceutical companies’ and other emerging biotech startups’ methods. Nivien’s goal is not to develop another expensive, risky drug that only works for a few people. The biotech company aims to combine develop new therapies that shut down the common defense mechanisms of cancer cells, allowing for existing treatment options to be more effective in driving a patient’s cancer into remission. Horwitz and Shah believe that by focusing on neutralizing a cancer cell’s ability to defend itself from treatment instead of creating a stronger drug to overwhelm the defective cell, they can treat a variety of cancers that share these exploitable defense mechanisms.
Treating any type of cancer is tricky and costly. For example, the average cost of care for treating pancreatic cancer is roughly $62,000 from start to finish. According to CNBC, the global cancer drug market size was $107 billion in 2016. These costs stem from the difficulties of treating cancer effectively. With standard treatment regimens of chemotherapy, cancer cells are able to utilize their common defense mechanisms to limit the effectiveness of the various drugs taken by the patient. Horwitz views these defense mechanisms as ‘escape routes’.
“Cancer cells use these ‘escape routes’ to avoid the main effect of chemotherapy, which is inducing cell death,” Horwitz says. “With our approach, we have a first hand view on how these escape routes evolve when a patient undergoes initial treatment.”
By observing how the cancer reacts to the first round of drugs, Nivien can take that data and design small molecules to block secondary and tertiary ‘escape routes’. Their approach allows them to effectively address the current first level defense mechanisms, giving them the opportunity to make these critical observations.
Their approach is somewhat similar to a Trojan Horse strategy — instead of killing cancer cells directly with a more potent drug, the two scientists study how cancer responds to treatment through its defenses, then design drugs to neutralize those barriers, resulting in more effective treatment through conventional chemotherapy.
In addition to their novel insights from chemistry bench work in the lab, they will also utilize computational biology to help them pore through thousands of patients’ sequenced DNA. Recent advancements in the computational power of these biology-purposed toolkits allow for a higher number of patients to be sequenced in a shorter amount of time. From these developments, Nivien is able to profile a wider range of patients in their quest to discover the commonalities of cancer’s ‘escape routes’ from a diverse biological dataset. Horwitz and Shah are working on treating a variety of cancers, but their main focus is treating pancreatic cancer to prove their approach yields fruitful results.
Nivien could not have developed its unique approach without two fresh, novel insights that were recently published. First, researchers discovered that a particular signaling pathway — a group of molecules work together in a specific sequence to control critical cell functions — called Hippo, plays a larger than previously thought role in the resistance of cancer cells. Specifically, the Hippo signaling pathway plays a role in controlling organ size, and when a mutation occurs in one of the key genes of the pathway, uncontrolled cell growth occurs, which is essentially cancer. Biology scholars have discovered that this cell pathway can be deactivated. The second key insight is that when the Hippo pathway is deactivated, the body’s natural immune response is enhanced.
These two insights joined together played a critical role in Nivien forming their current solution to improving cancer treatment. The team is securing patents to protect the intellectual property generated from their work and to bolster the defensibility of its solution against competitors. Their main competitor, Vivace Therapeutics, is producing a special type of antibody to inhibit cancerous cells. The main difference between Nivien’s and Vivace’s approach lies in their overarching strategy. With the latter’s method, these antibodies can bind to the defective cells and shut them down, but further random cell mutations could decrease the effectiveness of their drug as the cancer cells adapt to this kind of treatment.
Nivien’s approach focuses on observing how cancer cells react to an initial dosage of treatment and develops small molecules that are tailored to inhibit cancer cells’ new defense mechanisms as it adapts to new drugs. A potential drawback of Nivien’s approach is the evolution of the patient’s cancer may require a complex cocktail of tailored drugs to combat its various primary, secondary, and tertiary defense mechanisms. However, the team is willing to take that risk to improve both survival and quality-of-life of the patient and reduce the overall costs of treating cancer for the patient and the healthcare system.
Innovation and funding in biotech happen so quickly that Horwitz decided to drop out a semester before graduating from Harvard to pursue this work further in a commercial setting. For now, it seems like the right choice for him and his co-founder, Shah.
“Venture capital firms focused on biotech mostly pour money into startups developing new immunotherapy drugs,” Shah says. “However, we are focused on enhancing chemotherapy through the drugs we develop by increasing the therapeutic window and decreasing the toxic side-effects of treatment.”
Despite the team’s unconventional approach, Nivien has been accepted into IndieBio, one of the world’s leading life science startup accelerators, receiving $250,000 in seed funding and crucial access to mentors and investors. Also, the team’s coffers have received additional padding through another $250,000 investment from Third Kind Venture Capital.
Capital isn’t only resource Nivien has at its disposal. The startup’s strategic partnerships with Harvard Medical School, Charles River Labs, a specialized contract lab providing pre-clinical and clinical laboratory services to outside parties, and Reverie Labs, a machine learning startup focused on developing algorithms that leverage data to expedite the drug discovery process, help solidify the nascent firm’s advantages over competitors. More importantly, these partnerships signify the belief of outside parties that Nivien may have the right approach in treating cancer more effectively.
Some may wonder why these two young life science entrepreneurs are founding a biotech startup. Horwitz and Shah realize that they are not the typical founders of a biotech company, which is why they have hired excellent scientists such as Dr. Dharmendra Singh (Nivien’s SVP of Cancer Biology), a former senior research associate at Houston Methodist Research Institute, UCLA, and postdoctoral fellow at the National Institute of Health, and Dr. W. Ken Fang (Nivien’s SVP of Medicinal Chemistry), a former principal scientist at Allergan. In addition to such a deep roster of talent, the startup has a deeply experienced scientific advisory board to guide their research and rigorously check their results.
Only time will tell if Horwitz, Shah, and the rest of Nivien Therapeutics has struck gold when it comes to treating various types of cancer.
If Helen wore the face that launched a thousand ships, cancer was the problem that gave rise to a thousand solutions.
And Nivien Therapeutics might have the right one.
This post originally appeared in Forbes.