CIRM Board Approves Two New Discovery Research Projects for COVID-19

Dr. Karen Christman (left) and Dr. Lili Yang (right)

This past Friday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved two new discovery research project as part of the $5 million in emergency funding for COVID-19 related projects.  This brings the number of COVID-19 projects CIRM is supporting to 17, including three clinical trials.

$249,974 was awarded to Dr. Karen Christman at UC San Diego to develop a treatment for Acute Respiratory Distress Syndrome (ARDS), a life-threatening lung injury that occurs when fluid leaks into the lungs and is prevalent in COVID-19 patients.  Dr. Christman and her team will develop extracellular matrix (ECM) hydrogels, a kind of structure that provides support to surrounding cells.  The goal is to develop a treatment that can be delivered directly to site of injury, where the ECM would recruit stem cells, treat lung inflammation, and promote lung healing.

$250,000 was awarded to Dr. Lili Yang at UCLA to develop a treatment for COVID-19.  Dr. Yang and her team will use blood stem cells to create invariant natural killer T (iNKT) cells, a powerful kind of immune cell with the potential to clear virus infection and mitigate harmful inflammation.  The goal is to develop these iNKT cells as an off the shelf therapy to treat patients with COVID-19.

These awards are part of CIRM’s Quest Awards Program (DISC2), which promotes promising new technologies that could be translated to enable broad use and improve patient care.

“The harmful lung inflammation caused by COVID-19 can be dangerous and life threatening,” says Maria T. Millan, M.D., the President and CEO of CIRM. “Early stage discovery projects like the ones approved today are vital in developing treatments for patients severely affected by the novel coronavirus.”

Earlier in the week the Board also approved changes to both DISC2 and clinical trial stage projects (CLIN2). These were in recognition of the Agency’s remaining budget and operational timeline and the need to launch the awards as quickly as possible.

For DISC2 awards the changes include:

  • Award limit of $250,000
  • Maximum award duration of 12 months
  • Initiate projects within 30 days of approval
  • All proposals must provide a statement describing how their overall study plan and design has considered the influence of race, ethnicity, sex and gender diversity.
  • All proposals should discuss the limitations, advantages, and/or challenges in developing a product or tools that addresses the unmet medical needs of California’s diverse population, including underserved communities.

Under the CLIN2 awards, to help projects carry out a clinical trial, the changes include:

  • Adjust award limit to the following:
Applicant typePhase 1, Phase 1/2, Feasability Award CapPhase 2 Award CapPhase 3 Award Cap
Non-profit$9M$11.25M$7.5M
For-profit$6M$11.25M$7.5M
  • Adjust the award duration to not exceed 3 years with award completion no later than November 2023
  • Initiate projects within 30 days of approval
  • All proposals must include a written plan in the application for outreach and study participation by underserved and disproportionately affected populations. Priority will be given to projects with the highest quality plans in this regard.

The changes outlined above for CLIN2 awards do not apply to sickle cell disease projects expected to be funded under the CIRM/NHLBI Cure Sickle Cell Disease joint Initiative.

Research Targeting Prostate Cancer Gets Almost $4 Million Support from CIRM

Prostate cancer

A program hoping to supercharge a patient’s own immune system cells to attack and kill a treatment resistant form of prostate cancer was today awarded $3.99 million by the governing Board of the California Institute for Regenerative Medicine (CIRM)

In the U.S., prostate cancer is the second most common cause of cancer deaths in men.  An estimated 170,000 new cases are diagnosed each year and over 29,000 deaths are estimated in 2018.  Early stage prostate cancer is usually managed by surgery, radiation and/or hormone therapy. However, for men diagnosed with castrate-resistant metastatic prostate cancer (CRPC) these treatments often fail to work and the disease eventually proves fatal.

Poseida Therapeutics will be funded by CIRM to develop genetically engineered chimeric antigen receptor T cells (CAR-T) to treat metastatic CRPC. In cancer, there is a breakdown in the natural ability of immune T-cells to survey the body and recognize, bind to and kill cancerous cells. Poseida is engineering T cells and T memory stem cells to express a chimeric antigen receptor that arms these cells to more efficiently target, bind to and destroy the cancer cell. Millions of these cells are then grown in the laboratory and then re-infused into the patient. The CAR-T memory stem cells have the potential to persist long-term and kill residual cancer calls.

“This is a promising approach to an incurable disease where patients have few options,” says Maria T. Millan, M.D., President and CEO of CIRM. “The use of chimeric antigen receptor engineered T cells has led to impressive results in blood malignancies and a natural extension of this promising approach is to tackle currently untreatable solid malignancies, such as castrate resistant metastatic prostate cancer. CIRM is pleased to partner on this program and to add it to its portfolio that involves CAR T memory stem cells.”

Poseida Therapeutics plans to use the funding to complete the late-stage testing needed to apply to the Food and Drug Administration for the go-ahead to start a clinical trial in people.

Quest Awards

The CIRM Board also voted to approve investing $10 million for eight projects under its Discovery Quest Program. The Quest program promotes the discovery of promising new stem cell-based technologies that will be ready to move to the next level, the translational category, within two years, with an ultimate goal of improving patient care.

Among those approved for funding are:

  • Eric Adler at UC San Diego is using genetically modified blood stem cells to treat Danon Disease, a rare and fatal condition that affects the heart
  • Li Gan at the Gladstone Institutes will use induced pluripotent stem cells to develop a therapy for a familial form of dementia
  • Saul Priceman at City of Hope will use CAR-T therapy to develop a treatment for recurrent ovarian cancer

Because the amount of funding for the recommended applications exceeded the money set aside, the Application Subcommittee voted to approve partial funding for two projects, DISC2-11192 and DISC2-11109 and to recommend, at the next full Board meeting in October, that the projects get the remainder of the funds needed to complete their research.

The successful applications are:

 

APPLICATION

 

TITLE

 

INSTITUTION

CIRM COMMITTED FUNDING
DISC2-11131 Genetically Modified Hematopoietic Stem Cells for the

Treatment of Danon Disease

 

 

U.C San Diego

 

$1,393,200

 

DISC2-11157 Preclinical Development of An HSC-Engineered Off-

The-Shelf iNKT Cell Therapy for Cancer

 

 

U.C. Los Angeles

 

$1,404,000

DISC2-11036 Non-viral reprogramming of the endogenous TCRα

locus to direct stem memory T cells against shared

neoantigens in malignant gliomas

 

 

U.C. San Francisco

 

$900,000

DISC2-11175 Therapeutic immune tolerant human islet-like

organoids (HILOs) for Type 1 Diabetes

 

 

Salk Institute

 

$1,637,209

DISC2-11107 Chimeric Antigen Receptor-Engineered Stem/Memory

T Cells for the Treatment of Recurrent Ovarian Cancer

 

 

City of Hope

 

$1,381,104

DISC2-11165 Develop iPSC-derived microglia to treat progranulin-

deficient Frontotemporal Dementia

 

 

Gladstone Institutes

 

$1,553,923

DISC2-11192 Mesenchymal stem cell extracellular vesicles as

therapy for pulmonary fibrosis

 

 

U.C. San Diego

 

$865,282

DISC2-11109 Regenerative Thymic Tissues as Curative Cell

Therapy for Patients with 22q11 Deletion Syndrome

 

 

Stanford University

 

$865,282