Mass General Brigham Awards $1 Million to Biotech Breakthroughs

Game-changing biotech innovations include new delivery system for brain cancer therapeutics, better detection of potential pregnancy complications, single-handed central line placement device, and more.

BOSTON, MA – Ten biotech advancements from Mass General Brigham have been awarded Innovation Discovery Grants (IDG) in the 2022 round of awards for the highly competitive grant program. Each of the potential patient care and health care delivery breakthroughs will receive $100,000 toward ongoing development and future commercialization, based on the potential to improve health outcomes, meet articulated milestones, and attract follow-on investment as assessed by independent industry experts.

“Every day, Mass General Brigham researchers are working to translate innovation into clinical applications that improve outcomes for patients faced with challenging diseases,” said Ravi Thadhani, MD, Chief Academic Officer, Mass General Brigham. “The Innovation Discovery Grants support translation of biotech research from the lab to real-world products whereby they can help more patients.”

The Mass General Brigham Harvard faculty receiving this year’s IDG awards are:

• A novel Convection Enhanced Delivery system for brain malignancies
  Miles Cunningham, MD, PhD, McLean Hospital
  
  
• FastLine: Single-handed venous access device
  Hilary Gallin, MD, Massachusetts General Hospital
  
  
• Development of KRAS degraders in cancer
  Vidyasagar Koduri, MD, PhD, Brigham and Women’s Hospital
  
  
• Restoring tumor immunogenicity in glioblastoma multiforme (GBM)
  Choi-Fong Cho, PhD, Brigham and Women’s Hospital
  
  
• Developing first-in-class mRNA methyltransferase inhibitor
  Li Lan, MD, PhD, Massachusetts General Hospital 
  
  
• Auditory mirror therapy for tinnitus
  Clas Linnman, PhD, Spaulding Rehabilitation
  
  
• Noninvasive diagnosis of middle-ear pathologies
  Hamid Motallebzadeh, PhD, Massachusetts Eye and Ear 
  
  
• Small-molecule MMP inhibitors for allergic inflammation
  Jin Mo Park, PhD, Massachusetts General Hospital 
  
  
• Neutralizing antibody to FSTL3 as an immunotherapy in ovarian cancer
  David Pepin, PhD, Massachusetts General Hospital 
  
  
• Circulating microparticle proteins predict pregnancies complicated by placenta accreta spectrum
  Hope Yu, MD, Brigham and Women’s Hospital 

Since IDG’s inception in 2014, 65 research projects have been awarded a combined $4.2 million and, together, have raised more than $199 million to further their development. This includes 14 new companies actively developing IDG-supported technologies and 19 license agreements.

“Advancements in biotech are redefining the future of medicine,” said Mass General Brigham Chief Innovation Officer Chris Coburn. “These grants recognize the tremendous commitment to spark innovation throughout Mass General Brigham and translate invention to the front lines of care.”

The IDG awards were announced at the World Medical Innovation Forum (WMIF) in Boston. More than 1,000 health care leaders, industry executives, and investment experts are gathered at WMIF to explore the future of medicine in a 3-day program, this year focusing on gene and cell therapy. The Forum is presented by Mass General Brigham and Bank of America, bringing together two leading organizations with extensive health care expertise to advance medical breakthroughs for patients and support Boston’s continued growth as a global biotech and investment hub.

The following are descriptions of each of the 2022 IDG awards:

A novel Convection Enhanced Delivery system for brain malignancies

Miles Cunningham, MD, PhD, McLean Hospital

Convection Enhanced Delivery (CED) is a method in which a large volume of therapeutic agent under hydrostatic pressure is infused directly within diseased brain tissue. CED is being investigated primarily for glioblastoma multiforme (GBM), an aggressive brain cancer that leads to approximately 200,000 deaths worldwide each year. Typically, patients live only a few months following diagnosis. There have been no significant improvements in treatment for GBM in 40 years. The proposed CED system addresses conventional CED shortcomings by replacing a large, cumbersome delivery tube with multiple precision micro-cannulas. These small tubes are positioned strategically in 3-D arrays, using sophisticated surgical planning software and rapid prototyping to fabricate a patient-specific system within 1–2 days of diagnosis. GBM represents but one indication for this system; other indications include inoperable epilepsy and traumatic brain injury.

FastLine: Single-handed venous access device

Hilary Gallin, MD, Massachusetts General Hospital

FastLine is a device that enables placement of a central line with one hand using intuitive, ergonomic movements to enable real-time troubleshooting and allow the use of ultrasound in the other hand throughout the entire procedure. The device eliminates poorly controlled movements that occur with the traditional placement technique and is designed to maximize control and dexterity. It also aggregates almost every required component of the procedure into one device with a safety needle, increasing central line kit organization and decreasing risk of contamination or needlesticks. FastLine will reduce complications, decrease procedure time, improve the patient experience, and serve to reduce the $2 billion spent on managing patient injuries. arising from the 5 million central line placements in the U.S. alone each year.

Development of KRAS degraders in cancer

Vidyasagar Koduri, MD, PhD, Brigham and Women’s Hospital

Mutation in the KRAS (Kirsten Rat Sarcoma virus) gene are the main drivers of lung, colon, and pancreatic cancer, which, together, kill 230,000 annually in the U.S. Treatment regimens are arduous, only partially effective, and cost (in aggregate) hundreds of millions of dollars. The preponderance of data from studies in cell, animal, and patient-derived models of disease indicate that therapeutically targeting KRAS would be an enormous advance in the treatment of these cancers. The proposed research program uses a newly developed positive-selection screening platform as a tool to identify protein degraders of KRAS (rather than inhibitors) as potential therapeutic agents. This approach has been validated as a game-changer in other cancers, such as multiple myeloma.

Restoring tumor immunogenicity in glioblastoma multiforme (GBM)

Choi-Fong Cho, PhD, Brigham and Women’s Hospital

This program features a novel drug that may change the paradigm for glioblastoma (GBM) therapy. Traditional treatments for GBM (chemotherapy, radiation, and surgical resection) have remained unchanged for decades, and the prognosis for GBM patients is grim. While emerging cancer therapies (e.g., allogenic cell therapies) are being developed, so far, they remain unsuccessful in clinical trials, in addition to being very expensive and highly variable in outcomes between patients. This program has engineered and patented a new therapeutic that can cross the blood-brain barrier, induce tumor immunogenicity in models of GBM and other solid cancers, as well as synergize with cell therapies. Such a multi-pronged approach has never been tested in the clinic and could markedly improve outcomes in GBM while also improving the activity of cell therapy.

Developing first-in-class mRNA methyltransferase inhibitor

Li Lan, MD, PhD, Massachusetts General Hospital

The goal of this study is to develop IND-enabled compounds targeting mRNA methyltransferase and validate their effectiveness in cancer therapy. The ultimate goal is to target a newly identified mRNA-dependent repair pathway and mRNA methylating enzymes in DNA repair in cancer therapy. This could lead to effective therapeutic strategies for around 90 percent of breast and ovarian cancer patients without HRD, as well as effective therapeutic strategies for other cancers. These first-in-class mRNA methyltransferase inhibitors for cancer treatment have a high potential for the cancer drug market and the treatment of a large population of cancer patients.

Auditory mirror therapy for tinnitus

Clas Linnman, PhD, Spaulding Rehabilitation

Current health care cost for tinnitus (ringing in the ears) in the U.S. is estimated at $17 billion. About one in 10 adults suffer from tinnitus, yet there are no FDA-approved drugs or devices. The proposed technology provides a new type of treatment for tinnitus that is non-invasive, affordable, and low risk. This neuromodulatory therapy is based on disruption of multi-sensory integration. Like mirror box therapy for phantom pain, in this therapy, sound at the left ear is transmitted to the right ear canal, and sound at the right ear is transmitted to the left ear canal. Implemented in a wearable pair of headphones, a pilot trial of “auditory mirror therapy” (AMT) indicates that brief use of the headphones significantly and substantially reduced tinnitus. The effects of AMT will be verified in a larger, placebo-controlled study of persons with tinnitus. The technology can be implemented as a separate device, added to current hearing aids, or as a software application for microphone-equipped wireless earbuds with the potential to help many with tinnitus.

Noninvasive diagnosis of middle-ear pathologies

Hamid Motallebzadeh, PhD, Mass Eye and Ear

According to National Institute on Deafness and Other Communication Disorders, approximately 15% of American adults (37.5 million), aged 18 and older, report some trouble hearing, among which, over 50% of the cases are related to conductive hearing loss. Wideband tympanometry is a promising cost-effective tool for noninvasively probing the status of the ear. However, interpreting its complex outcome to provide reliable indicators of middle-ear pathologies has proven challenging. This project aims to automate objective differential diagnoses of middle-ear pathologies by taking advantage of powerful pattern-recognition capabilities of machine learning to infer details about the middle-ear status from clinical data. This tool could reduce the need for exploratory surgery, improve the specificity of preoperative preparations, and provide a low-cost tool for postoperative monitoring. This tool helps spot features that the human eye has difficulty identifying, which can help avoid subjective interpretations in differential diagnosis of the middle-ear and conductive pathologies.

Small-molecule MMP inhibitors for allergic inflammation

Jin Mo Park, PhD, Massachusetts General Hospital

Current allergy medications, ranging from corticosteroids to cytokine receptor-blocking antibodies to JAK inhibitors, are effective in only subsets of patients, produce partial responses, and often encounter treatment resistance. More importantly, they directly interfere with the workings of the immune system and can cause harmful side effects. The inadequacy of current medications to address these problems and the deficiency of new solutions prevent the pharmaceutical and health care industry from creating effective allergy treatment options for large patient populations. This project aims to develop small-molecule inhibitors of a specific protein-degrading enzyme as topical therapeutics for atopic dermatitis (AD), asthma, and other allergic inflammatory diseases. Preliminary data show that this enzyme plays a key role in driving allergic inflammation.

Neutralizing antibody to FSTL3 as an immunotherapy in ovarian cancer

David Pepin, PhD, Massachusetts General Hospital

High-grade serous ovarian cancer is the most lethal gynecologic malignancy, accounting for 70% of ovarian cancer-related deaths, and affecting over 14,000 women in 2020. The treatment options for these patients are limited, particularly for patients that do not respond to chemotherapy or PARP inhibitors, and the survival rates have remained low. The advent of immunotherapies, such as immune checkpoint blockade (ICB), has brought a paradigm shift in the treatment of many cancers, sometimes providing curative responses. Unfortunately, immune checkpoint blockade therapies have not been successful in ovarian cancer, which is generally resistant to these agents. Our technology consists of a neutralizing antibody to FSTL3, which we hypothesize drives this resistance, that would be used in combination with immune checkpoint blockade therapy and alongside the current standard of care for ovarian cancer. We expect that this technology will significantly increase the response rate of ovarian cancer to immune checkpoint therapies and lead to significantly better outcomes.

Circulating microparticle proteins predict pregnancies complicated by placenta accreta spectrum

Hope Yu, MD, Brigham and Women’s Hospital

Placenta accreta spectrum, or PAS, is a potentially life-threatening pregnancy complication that occurs in approximately 1 in every 1,000–2,000 pregnancies. There is no biomarker test for PAS currently, and diagnostics rely on imaging studies and assessment of clinical risk factors. Despite these efforts, approximately 50% of PAS cases remain unidentified prior to delivery. The proposed product is a blood test to assess a woman’s risk of PAS, using circulating microparticle (CMP) proteins. The research team has previously identified a CMP protein panel that distinguishes pregnancies affected by PAS from unaffected pregnancies. This test would be used at the end of the second trimester with a woman’s routine outpatient blood work. Implementation of a blood test using this CMP protein panel has potential to improve the antenatal detection of PAS and is critical in global efforts to reduce maternal morbidity and mortality.

Mass General Brigham is the nation’s largest academic research enterprise. More than 150 life science and biotechnology companies have been established in Massachusetts as a result of the more than $2 billion in government funded and privately sponsored research that Mass General Brigham attracts every year. The groundbreaking research performed at Mass General Brigham is integral to developing and commercializing life-changing therapies which sustains Massachusetts’ competitive advantage in the innovation economy.

About the World Medical Innovation Forum

The World Medical Innovation Forum was established in 2015 in response to the intensifying transformation of health care and its impact on innovation. The Forum is rooted in the belief that no matter the magnitude of change, the center of health care needs to be a shared, fundamental commitment to collaborative innovation – industry and academia working together to improve patient lives.