The Daedalus Fund for Innovation, a unique de-risking program of Weill Cornell Medicine Enterprise Innovation, announced its recipients for funding this year.
Dr. Mohammed Fouda, Dr. Paraskevi (Evi) Giannakakou, Dr. Shahin Rafii and Dr. Jonathan Villena-Vargas were selected for the Daedalus award among 25 total proposals which were reviewed by an independent external scientific advisory committee of recognized leaders from the biopharmaceutical and venture capital communities. All awardees will use the funding for additional proof-of-concept studies that will generate more data and refine their technologies to make better candidates for therapeutics or medical devices.
The Daedalus Fund for Innovation’s mission is to bridge the funding and development gap and ensure that academic research which is still considered too early for industry or venture investment has the resources necessary to accelerate projects until they can attract investment and commercialization partners. Awardees are eligible for two levels of funding: $100,000 for one year or $400,000 for two years, with the second year contingent upon reaching pre-defined milestones.
“The Daedalus Fund for Innovation is designed to advance early-stage translational research projects that have clear, relatively near-term commercial potential,” said Dr. Lisa Placanica, senior managing director, Center for Technology Licensing at Weill Cornell Medicine. “We are excited to support our awardees with this funding opportunity so that they can advance their technologies through the next inflection point in order to strengthen the technologies’ commercial positioning and value with further data validation.”
Dr. Mohammed Fouda, Fellow in Neurological Surgery
Magnet Actuated Cranial (M.A.C) Bioresorbable Distraction System
Syndromic craniosynostosis, constituting 15 percent of all cases of craniosynostosis in children, is characterized by skull bones that have fused together too early in development. As a result, the skull can be misshapen to accommodate the growing brain after birth. The primary objectives in the surgical management of syndromic synostosis include expanding the volume of the skull, reducing elevated intracranial pressure (ICP), orbital protection and restoring normal midface and mandibular anatomy.
Distraction osteogenesis (DO) is an important treatment option facilitating bone formation between bony segments of the skull that are separated through controlled traction. Current standard of care cranial vault distraction devices require external activation ports that protrude through the skin and can lead to numerous complications including infection, repeated surgeries and blood loss.
Dr. Fouda and his team have engineered a novel distraction system for syndromic craniosynostosis, which is made of bioresorbable material and does not require external activation ports. The distractor utilizes a magnet and spring-like mechanism to enable more precise movements in the bone segments for safer and less costly surgical treatment.
Dr. Fouda will use the Daedalus award to advance the device prototype to preclinical testing. “This substantial funding will facilitate the transition of the M.A.C. distraction system from a prototype stage to a commercially viable product, presenting a potential for strategic partnerships and licensing agreements with industry stakeholders,” Dr Fouda says. “Such collaborations could deliver a more streamlined and economically feasible neurosurgical solution to our patients, particularly within resource-constrained regions globally.”
Dr. Paraskevi (Evi) Giannakakou, Professor of Pharmacology in Medicine
First-In-Class Dual AR-V7/AR-fl Molecular Glue Degrader for Prostate Cancer Treatment
Prostate cancer (PC) is the most diagnosed cancer among men and second leading cause of cancer death in men in the United States. This cancer is driven by abnormal androgen receptor (AR) signaling, so the mainstay of treatment has been androgen deprivation therapy, hormone therapy that reduces testosterone levels. However, PC often metastasizes to other organs and advances to castration-resistant PC (mCRPC) as a result of testosterone-lowering treatments stop working. This is due to changes in androgen receptor splicing that creates a truncated version of the androgen receptor called AR-V7, which cannot bind testosterone. Expression of AR-V7 is associated with poor survival outcomes and resistance to standard of care AR signaling inhibitors, highlighting the clinical unmet need for a dual inhibitor that targets both normal, full-length AR (i.e. AR-fl) and splice variant AR-V7.
Dr. Giannakakou and her team have determined the biochemical features of AR-V7 that can be selectively targeted by small molecule degrader compounds. Initial lead compounds have been able to degrade both full-length AR (AR-fl) and AR-V7, as well as reverse the enzalutamide resistance in human PC cell lines. Enzalutamide is a class of medications called androgen receptor inhibitors that can block testosterone from binding the receptor and one of the few treatment options for PC patients.
With the Daedalus award, Dr. Giannakakou will optimize the drug-like properties of their lead degrader compound through medicinal chemistry and confirm the reversal of enzalutamide resistance in vivo, the main clinical challenge for mCRPC patients. The team hopes this data package will facilitate the further clinical development and commercialization of their novel AR-V7/AR-fl degrader platform.
“I am very grateful for Daedalus funding because it is coming at a critical point in our project where we are performing key in vivo experiments that will help de-risk our technology,” Dr. Giannakakou says. “It will also help with making our technology more attractive to external stakeholders who can help us accelerate the clinical development of our compound.”
Dr. Shahin Rafii, Arthur B. Belfer Professor in Genetic Medicine and Professor of Medicine
Subcutaneous Transplantation of Islet-Specific Endothelial Cell Vascularized Islets to Treat Diabetes
Type 1 diabetes (T1D) is an autoimmune disease that leads to the destruction of insulin-producing beta cells in pancreatic islets, thus eradicating glucose-stimulated insulin secretion and necessitating daily insulin injections. While islet transplantation holds promise as a potential cure for T1D, its application is hampered by the scarcity of islet donors and the low survival rate of transplanted islets. An alternative to donated islets is mass production of pluripotent stem cell-derived islets (SC-islets) using recent manufacturing innovations that have produced cell therapies. However, current clinical protocols have associated risks, such as thrombosis, inflammation and graft failure.
To overcome these obstacles, Dr. Rafii and his laboratory have engineered islet-specific endothelial cells (ISECs)—the building blocks of blood vessels—that can readily adapt to and support SC-islets after they are transplanted. This new procedure should allow improved transplantation and engraftment under the skin. The ISEC derived blood vessels can supply beta cells in the pancreas with growth factors that improve glucose-stimulated insulin secretion and increase survival of engrafted islets.
The commercial opportunity for this technology is evidenced by a growing T1D therapeutics market, which is estimated to exceed 10 billion dollars in the next five years. “Given the current hurdles in securing funding for pre-clinical studies, the Daedalus Fund is highly timely and instrumental for expediting the execution of key pre-clinical experiments to accelerate the transition to the clinic,” says Dr. Rafii. “Specifically, it will enable us to enhance the procurement of stem cell-derived islets and to scale up the manufacturing of vascularized islets.” Dr. Rafii and his team hope to advance this project towards an Investigational New Drug (IND) application and initiation of human clinical trials.
Dr. Jonathan Villena-Vargas, Assistant Professor of Clinical Cardiothoracic Surgery
T-Cells Selected from Lymph Node Acquisition for Adoptive Cell Treatment of Solid Tumors
Chimeric antigen receptor (CAR) T-cell immunotherapies have shown tremendous clinical success in blood cancers, as evidenced by six FDA approvals and initiatives to establish CAR T as a first-line therapy. This treatment involves collecting T cells from the patient's blood, growing them in a lab, and then infusing them back into the patient. The engineered T cells recognize and attack cancer cells based on their characteristic antigens, the proteins or other molecules specific to the cancer cells. However, CAR T has not been effective with solid tumors partly because their antigens are highly variable and lack a single, ubiquitous targetable antigen (such as CD19 in blood cancers).
Furthermore, the engineered, peripheral blood T cells have difficulty navigating to and infiltrating tumors, which decreases their therapeutic efficacy. By studying the T cell clonal dynamics of non-small cell lung cancer (NSCLC) patients, Dr. Villena-Vargas has identified a unique subset of stem-like memory (SCM) CD8+ T cells within the tumor draining lymph nodes (tdLN). Compared to peripheral blood-derived T cells, SCM T cells extracted from this anatomical niche harbor a broader spectrum of cells capable of recognizing multiple tumor antigens to overcome the “antigen escape” properties of solid tumors — a common way for tumors to avoid being recognized and destroyed by CAR-T cells.
Dr. Villena-Vargas is developing a new approach to cancer immunotherapy that leverages lymph-node-derived T cells engineered to fight solid tumors, specifically targeting non-small cell lung cancer (NSCLC). This innovative method could potentially overcome the limitations faced by current adoptive cell therapies. "We have identified that the lymph nodes are immune reservoirs of unique pluripotent T cell subsets that recognize tumor cells. These cells may provide a possible tactic against 'antigen escape'," Dr. Villena-Vargas explains. With the Daedalus funding, he aims to develop a high-throughput manufacturing process that follows GMP (Good Manufacturing Practice) standards and minimizes variability, which is essential for producing clinical-grade cells. Establishing a viable, T-cell production process is a critical step in fulfilling Investigational New Drug (IND) criteria for future clinical trials. The first goal is to treat immunotherapy-resistant metastatic NSCLC patients, who comprise more than 50 percent of the 125,000 new lung cancer diagnoses annually. "With rapid advancements in cell engineering and the feasibility of surgical adoptive cell therapy approaches, we are optimistic that this approach holds the potential to overcome several solid tumor barriers and improve the survival of lung cancer patients," Dr. Villena-Vargas adds.