Asked & Answered: Follow the Biology

Abstract

Adam Rosenthal, CEO and founder of Star Therapeutics

Adam Rosenthal is the CEO and founder of Star Therapeutics, a biotechnology company with a mission to develop life-changing therapies for as many rare diseases as possible. The company's engine for innovation starts with identifying multiple rare diseases that share a common biology and then discovering novel therapeutics that can treat these diseases with a single therapy. Star consists of a family of companies, each focused on a specific area of biology, developing first-in-class therapies with the potential to target multiple diseases.

Rosenthal recently spoke with Inside Precision Medicine's editor in chief, Damian Doherty, about the company's unique approach to rare diseases and its first two spin outs—Electra Therapeutics and Vega Therapeutics—each focused on a distinct biology shared across multiple diseases.

Doherty: What is Star Therapeutics' approach to drug discovery and how does it set you apart from other drug companies?

Rosenthal: Most other drug development efforts start with a specific biological target and then find a relevant disease, or focus at the onset on researching a single disease. In these cases, if the original hypothesis can't be confirmed in that one disease, the new drug idea may be abandoned. Pharma companies' archives are full of molecules derived from thoughtful approaches towards druggable pathways, ultimately discarded due to a singular focus on a specific disease.

At Star Therapeutics, we take a unique approach and start by exploring constellations of numerous diseases and looking for common pathobiology across them. This gives us multiple shots on goal–the discovery of a single therapy that targets a fundamental disease driver across numerous diseases. Even if the drug candidate or pathway turns out to not be optimal for disease A, it could very well be optimal for diseases B and C and so on. With this strategy, we follow the biology to uncover key pathways that open up multiple potential opportunities to maximize the therapeutic potential of any given drug candidate. This allows us to build a program centered around numerous diseases and dig deep into novel biology. I'm proud of the fact that all of our programs were generated internally, from our own ideas, and we diligently followed the biology along the way. Two of our programs that started as ideas are now clinical stage.

The Star Therapeutics team recently enjoyed a company outing at a San Francisco Giants game while supporting patients with rare diseases.

Doherty: Tell me about your experience in rare diseases.

Rosenthal: At a previous company, True North Therapeutics, I and several members of the Star leadership team developed a deep understanding of a pathway in the complement system and identified numerous applicable diseases, including a rare hematologic condition called cold agglutinin disease (CAD). Despite CAD being a disease with significant morbidity and potential to be life-threatening, there was a lack of awareness of this true disease burden and no approved treatments available. Our drug discovery and development efforts at True North planted the seeds (prior to acquisition by Bioverativ in 2017 and subsequently Sanofi in 2018) for the FDA approval of ENJAYMO (sutimlimab) in February 2022 as the first approved treatment for CAD.

We were inspired by this experience and wanted to repeat the success achieved with our programs at True North. To date, we have spun out our first two companies, Electra Therapeutics and Vega Therapeutics from Star. Each clinical stage company is focusing on a specific area of biology to develop first-in-class therapies that can address multiple diseases with high unmet need.

Doherty: What is the area of biology focused on and uncovered by Electra Therapeutics, the first company spun out of Star?

Rosenthal: Rare hematologic diseases represented a natural starting point for us to follow the biology to find nodes for treating multiple diseases. From our time at True North, we understood the principal biological processes, the clinical development path, and, importantly, many of the key opinion leaders who could be sounding boards for our ideas. We compiled a list of rare diseases in hematology and went to work evaluating these diseases one at a time to identify the mechanisms driving each. We dug into the literature and had discussions with experts about what we found.

We identified signal regulatory protein (SIRP) as a probable node to target numerous diseases and asked questions that could lead us to a drug candidate and a first disease indication. We identified and explored a rare disease called secondary hemophagocytic lymphohistiocytosis (sHLH), a life-threatening hyperinflammatory condition that currently has no approved therapies. In following the biology, we also identified numerous other diseases beyond hematology that may be addressed through targeting SIRP and are currently exploring multiple immunological disorders.

Despite collectively affecting up to 30 million Americans, many individual rare diseases go unnoticed, without cure or adequate treatments. Star Therapeutics takes a unique approach to address the unmet need in this “long tail of disease” by honing in on common pathobiology shared by multiple conditions and developing drug candidates that have potential to treat numerous rare diseases.

Electra Therapeutics, the first company to be spun out of Star Therapeutics and launched in 2022, is taking a first-in-class approach to target SIRP to deplete pathological immune cells. Electra's lead candidate, ELA026, is an antibody that can deplete SIRP-expressing myeloid and T cells, the principal cells responsible for driving disease in sHLH. It is currently in a Phase 1b global study in sHLH patients. Beyond ELA026, we have additional preclinical programs aimed at immunological diseases and cancer.

Doherty: The second company spun out by Star was recently announced. What is the focus of Vega Therapeutics?

Rosenthal: Vega spun out from Star Therapeutics to bring novel therapies for rare blood disorders with unmet patient needs, starting with von Willebrand disease (VWD). People with VWD either have defective or low levels of von Willebrand factor, a protein that helps blood clot. VWD causes severe bleeding that can damage organs and lead to significant impact on patients' daily lives. While other bleeding disorders, such as hemophilia, have benefited from new treatment options that include effective and patient-friendly antibody therapies, drug innovation for VWD has lagged.

At Vega, we see a future where VWD patients have a treatment option that better meets their needs. We aim to bring a new paradigm to VWD to address the limitations of current treatments, which include factor replacement therapies that may require frequent IV infusions.

Vega has developed its lead product candidate, VGA039, to be the first purpose-built antibody therapy for VWD. VGA039 is a monoclonal antibody directed against Protein S to specifically address the underlying defects in the coagulation cascade caused by VWD, which lead to uncontrolled bleeding. VGA039's novel mechanism at restoring proper clotting can be applied to numerous other bleeding disorders beyond VWD, making it a potential universal hemostatic therapy.

Vega has generated data demonstrating preclinical efficacy of VGA039 in various bleeding disorders, including in vivo proof-of-concept in VWD. Studies have also shown VGA039's potential for infrequent subcutaneous dosing. Based on these findings, we are progressing VGA039 into clinical studies, which will initiate in early 2023.

Doherty: What's in the stars for Star Therapeutics?

Rosenthal: Our mission at Star is to develop life-changing treatments for patients. This translates to an unwavering pursuit to understand the science and to uncover opportunities to make an impact. We are working with great urgency to advance our programs, including studying ELA026 and VGA039 in clinical trials and generating additional drug candidates from our preclinical programs.

In addition to existing programs, we are continuing to evaluate internal ideas for new programs and possible in-licensing opportunities. Following our model, new programs may lead to new “stars” to be added to our constellation of companies.