Prime Time for Rocket

Rocket Pharmaceuticals, a company that specializes in developing genetic therapies for rare childhood disorders, just got a big boost from the European Medicines Agency (EMA). They were given a Priority Medicines (PRIME) designation for their therapy for Leukocyte Adhesion Deficiency-1 (LAD-1).

CIRM is funding ($6.56 million) Rocket’s clinical trial for LAD-I, an immune disorder that leaves patients vulnerable to repeated infections that often results in death within the first two years of life. The therapy involves taking some of the child’s own blood stem cells and, in the lab, correcting the mutation that causes LAD-I, then returning those cells to the patient. Hopefully those blood stem cells then create a new, healthy blood supply and repair the immune system.

The therapy, called RP-L201, is already showing promise in the clinical trial, hence the PRIME designation. The program was set up to help speed up development and evaluation of therapies that could help patients who have limited treatment options. Getting a PRIME designation means it is considered a priority by EMA and could reach patients sooner.

In the US, Rocket has won similar recognition from the Food and Drug Administration (FDA) and has been granted Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric Disease, and Fast Track designations.

In a news release Kinnari Patel, President and Chief Operating Officer of Rocket, said the designation showed that regulators understand the urgent need to develop a therapy for patients with LAD-1. “More than half of LAD-I patients suffer with a severe variant in which mortality occurs in up to 75% of young children who don’t receive a successful bone marrow transplant by the age of two. Securing all possible accelerated designations will enable us to collaborate with both the FDA and EMA to speed the development and delivery of a potential treatment for these patients.  We look forward to sharing initial Phase 2 data from our potentially registration-enabling LAD-I trial in the second quarter of 2021.”

That trial has now completed enrolling patients (nine altogether) but their treatments are not yet complete. LAD-1 patients with severe disease have low levels of a key protein called CD18, usually less than 2%. Of the first three patients treated in this trial CD18 levels are all higher than the 4-10% threshold considered necessary for these children to survive into adulthood. Another encouraging sign is that there were no serious side effects from the therapy.

Obviously there is still a long way to go before we know if this therapy really works, but the PRIME designation – along with the similar ones in the US – are recognition that this is a very promising start.

Going the extra mile to save a patient’s life

You can tell an awful lot about a company by the people it hires and the ability it gives them to do their job in an ethical, principled way. By that measure Rocket Pharma is a pretty darn cool company.

Rocket Pharma is running a CIRM-funded clinical trial for Leukocyte Adhesion Deficiency-I (LAD-I), a rare genetic immune disorder that leaves patients vulnerable to repeated infections that often results in death within the first two years of life. The therapy involves taking some of the child’s own blood stem cells and, in the lab, correcting the mutation that causes LAD-I, then returning those cells to the patient. Hopefully those blood stem cells then create a new, healthy blood supply and repair the immune system.

So far, they have treated the majority of the nine patients in this Phase 1/2 clinical trial. Here’s the story of three of those children, all from the same family. Every patient’s path to the treatment has been uniquely challenging. For one family, it’s been a long, rough road, but one that shows how committed Rocket Pharma (Rocket) is to helping people in need.

The patient, a young girl, is from India. The family has already lost one child to what was almost certainly LAD-I, and now they faced the very real prospect of losing their daughter too. She had already suffered numerous infections and the future looked bleak. Fortunately, the team at Rocket heard about her and decided they wanted to help enroll her in their clinical trial.

Dr. Gayatri Rao, Rocket Pharmaceuticals

Dr. Gayatri Rao, the Global Program Head for the LAD-I therapy, this patient was about 6 months old when they heard about her: “She had already been in and out of the hospital numerous times so the family were really interested in enrolling the patient. But getting the family to the US was daunting.”

Over the course of several months, the team at Rocket helped navigate the complicated immigration process. Because the parents and child would need to make several trips to the US for treatment and follow-up exams they would need multiple-entry visas. “Just to get all the paper work necessary was a monumental task. Everything had to be translated because the family didn’t speak English. By the time the family flew to Delhi for their visa interview they had a dossier that filled a 3 inch binder.”  Rocket worked closely with partners in India to provide the family on-the-ground support every step of the way.  To help ensure the family received the visas they needed, Rocket also reached out to members of Congress and six members wrote in support of the family’s application.

Finally, everything fell into place. The family had the visas, all the travel arrangements were made. The Rocket team had even found an apartment near the UCLA campus where the family would stay during the treatment and stocked it with Indian food.

But on the eve of their flight to the US, the coronavirus pandemic hit. International flights were cancelled. Borders were closed. A year of work was put on hold and, more important, the little girl’s life hung in the balance.

Over the course of the next few months the little girl suffered several infections and had to be hospitalized. The family caught COVID and had to undergo quarantine till they recovered. But still the Rocket team kept working on a plan to bring them to the US. Finally, in late January, as vaccines became available and international flights opened up once again, the family were able to come to the US. One west-coast based Rocket team member even made sure that upon arriving to the apartment in UCLA, there was a home-cooked meal, a kitchen stocked with groceries, and handmade cards welcoming them to help transition the family into their new temporary “home.” They are now in living in that apartment near UCLA, waiting for the treatment to start.

Gayatri says it would have been easy to say: “this is too hard” and try to find another patient in the trial, but no one at Rocket wanted to do that: “Once a patient gets identified, we feel like we know them and the team feels invested in doing everything we can for them. We know it may not work out. But at the end of the day, we recognize that this child often has no other choices, and that motivates us to keep going despite the challenges.  If anything, this experience has taught us that with persistence and creativity, we can surmount these challenges.”

Maybe doing the right thing brings its own rewards, because this earlier this month Rocket was granted Regenerative Medicine Advanced Therapy (RMAT) designation for their treatment for LAD-I. This is a big deal because it means the therapy has already shown it appears to be safe and potentially beneficial to patients, so the designation means that if it continues to be safe and effective it may be eligible for a faster, more streamlined approval process. And that means it can get to the patients who need it, outside of a clinical trial, faster.

Positive results from CIRM-funded LAD-I trial presented at the 62nd American Society of Hematology Annual Meeting

Gaurav Shah, M.D., CEO and President of Rocket Pharmaceuticals

Leukocyte Adhesion Deficiency-I (LAD-I) is a rare pediatric disease caused by a mutation in a specific gene that causes low levels of a protein called CD18. Due to low levels of CD18, the adhesion of immune cells is affected, which negatively impacts the body’s ability to combat infections.

Rocket Pharmaceuticals is conducting a CIRM-funded ($6.56 M) clinical trial that is testing a treatment that uses a gene therapy called RP-L201. The therapy uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient. The goal is to establish functional immune cells, enabling the body to combat infections. Previous studies have indicated that an increase in CD18 to 4-10% is associated with survival into adulthood. 

The company presented interim data from the trial at the 62nd American Society of Hematology (ASH) Annual Meeting in the form of an oral presentation. The data presented is from three pediatric patients with severe LAD-I, which is defined by CD18 expression of less than 2%. The patients were all treated with RP-L201. Patient One was 9-years of age at enrollment and had been followed for 12-months as of a cutoff date of November 2020. Patient Two was 3-years of age at enrollment and had been followed for over 6-months. Patient Three was 7-months of age at enrollment and was recently treated with RP-L201.

Key highlights from the presentation include:

  • RP-L201 was well tolerated, no safety issues reported with infusion or post-treatment
  • All patients achieved hematopoietic (blood) reconstitution within 5-weeks
    • 12 months post-treatment, Patient One demonstrated durable CD18 expression of approximately 40%,
    • 6-months post-treatment, Patient Two demonstrated CD18 expression of 23%
    • 2-months post-treatment, Patient Three demonstrated CD18 expression of 76%

In a press release from Rocket, Gaurav Shah, M.D., CEO and President of Rocket, expressed excitement about these results.

“…we continue to see encouraging evidence of efficacy for RP-L201 for the treatment of LAD-I. Patients have shown sustained CD18 expression of 23% to 40%, far exceeding the 4-10% threshold associated with survival into adulthood…”

To view the presentations at the conclusion of the oral presentation, click the link here.

CIRM Board Approves Four New Clinical Trials

A breakdown of CIRM’s clinical trials by disease area

This past Thursday the governing Board of the California Institute for Regenerative Medicine (CIRM) approved four new clinical trials in addition to ten new discovery research awards.

These new awards bring the total number of CIRM-funded clinical trials to 68.  Additionally, these new additions have allowed the state agency to exceed the goal of commencing 50 new trials outlined in its five year strategic plan.

$8,970,732 was awarded to Dr. Steven Deeks at the University of California San Francisco (UCSF) to conduct a clinical trial that modifies a patient’s own immune cells in order to treat and potentially cure HIV. 

Current treatment of HIV involves the use of long-term antiretroviral therapy (ART).  However, many people are not able to access and adhere to long-term ART.

Dr. Deeks and his team will take a patient’s blood and extract T cells, a type of immune cell.  The T cells are then genetically modified to express two different chimeric antigen receptors (CAR), which enable the newly created duoCAR-T cells to recognize and destroy HIV infected cells.  The modified T cells are then reintroduced back into the patient.

The goal of this one time therapy is to act as a long-term control of HIV with patients no longer needing to take ART, in effect a form of HIV cure.  This approach would also address the needs of those who are not able to respond to current approaches, which is estimated to be 50% of those affected by HIV globally. 

$3,728,485 was awarded to Dr. Gayatri Rao from Rocket Pharmaceuticals to conduct a clinical trial using a gene therapy for infantile malignant osteopetrosis (IMO), a rare and life-threatening disorder that develops in infancy.  IMO is caused by defective bone cell function, which results in blindness, deafness, bone marrow failure, and death very early in life. 

The trial will use a gene therapy that targets IMO caused by mutations in the TCIRG1 gene.  The team will take a young child’s own blood stem cells and inserting a functional version of the TCIRG1 gene.  The newly corrected blood stem cells are then introduced back into the child, with the hope of halting or preventing the progression of IMO in young children before much damage can occur. 

Rocket Pharmaceuticals has used the same gene therapy approach for modifying blood stem cells in a separate CIRM funded trial for a rare pediatric disease, which has shown promising results.

$8,996,474 was awarded to Dr. Diana Farmer at UC Davis to conduct a clinical trial of in utero repair of myelomeningocele (MMC), the most severe form of spina bifida.  MMC is a birth defect that occurs due to incomplete closure of the developing spinal cord, resulting in neurological damage to the exposed cord.  This damage leads to lifelong lower body paralysis, and bladder and bowel dysfunction.

Dr. Farmer and her team will use placenta tissue to generate mesenchymal stem cells (MSCs).  The newly generated MSCs will be seeded onto an FDA approved dural graft and the product will be applied to the spinal cord while the infant is still developing in the womb.  The goal of this therapy is to help promote proper spinal cord formation and improve motor function, bladder function, and bowel function. 

The clinical trial builds upon the work of CIRM funded preclinical research.

$8,333,581 was awarded to Dr. David Williams at Boston Children’s Hospital to conduct a gene therapy clinical trial for sickle cell disease (SCD).  This is the second project that is part of an agreement between CIRM and the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, to co-fund cell and gene therapy programs under the NHLBI’s  “Cure Sickle Cell” Initiative.  The goal of this agreement is to markedly accelerate clinical development of cell and gene therapies to cure SCD.

SCD is an inherited disease caused by a single gene mutation resulting in abnormal hemoglobin, which causes red blood cells to ‘sickle’ in shape.  Sickling of red blood cells clogs blood vessels and leads to progressive organ damage, pain crises, reduced quality of life, and early death. 

The team will take a patient’s own blood stem cells and insert a novel engineered gene to silence abnormal hemoglobin and induce normal fetal hemoglobin expression.  The modified blood stem cells will then be reintroduced back into the patient.  The goal of this therapy is to aid in the production of normal shaped red blood cells, thereby reducing the severity of the disease.

“Today is a momentus occasion as CIRM reaches 51 new clinical trials, surpassing one of the goals outlined in its five year strategic plan,” says Maria T. Millan, M.D., President and CEO of CIRM.  “These four new trials, which implement innovative approaches in the field of regenerative medicine, reflect CIRM’s ever expanding and diverse clinical portfolio.”

The Board also approved ten awards that are part of CIRM’s Quest Awards Prgoram (DISC2), which promote promising new technologies that could be translated to enable broad use and improve patient care.

The awards are summarized in the table below:

  APPLICATION  TITLE  INSTITUTION  AWARD AMOUNT  
    DISC2-12169  Human-induced pluripotent stem cell-derived glial enriched progenitors to treat white matter stroke and vascular dementia.  UCLA  $250,000
  DISC2-12170Development of COVID-19 Antiviral Therapy Using Human iPSC-Derived Lung Organoids  UC San Diego  $250,000
  DISC2-12111Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia  UCLA  $250,000
  DISC2-12158Development of a SYF2 antisense oligonucleotide (ASO) treatment for ALSUniversity of Southern California  $249,997
    DISC2-12124Dual angiogenic and immunomodulating nanotechnology for subcutaneous stem cell derived islet transplantation for the treatment of diabetes  Lundquist Institute  $250,000
  DISC2-12105Human iPSC-derived chimeric antigen receptor-expressing macrophages for cancer treatment  UC San Diego  $250,000
  DISC2-12164Optimization of a human interneuron cell therapy for traumatic brain injury  UC Irvine  $250,000
  DISC2-12172Combating COVID-19 using human PSC-derived NK cells  City of Hope  $249,998
  DISC2-12126The First Orally Delivered Cell Therapy for the Treatment of Inflammatory Bowel Disease  Vitabolus Inc.  $249,000
    DISC2-12130Transplantation of Pluripotent Stem Cell Derived Microglia for the Treatment of Adult-onset Leukoencephalopathy (HDLS/ALSP)  UC Irvine  $249,968

CIRM funded trial for LAD-I announces positive results

Leukocyte Adhesion Deficiency-I (LAD-I) is a rare pediatric disease caused by a mutation in a specific gene that causes low levels of a protein called CD18. Due to low levels of CD18, the adhesion of immune cells is affected, which negatively impacts the body’s ability to combat infections.

Rocket Pharmaceuticals has announced positive results from a CIRM-funded clinical trial that is testing a treatment that uses a gene therapy called RP-L201. The therapy uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient. The goal is to establish functional immune cells, enabling the body to combat infections.  

The two patients enrolled in the CIRM funded trial have shown restored levels of CD18. Previous studies have indicated that an increase in CD18 to 4-10% is associated with survival into adulthood. The two patients demonstrated CD18 levels that exceeded this threshold.

In a news release, Jonathan Schwartz, M.D. Chief Medical Officer and Senior Vice President of Rocket, elaborated on these positive results.

“Patients with LAD-I have markedly diminished expression of the integrin CD18 and suffer from life-threatening bacterial and fungal infections. Natural history studies indicate that an increase in CD18 expression to 4-10% is associated with survival into adulthood. The two patients enrolled in our Phase 1 trial demonstrated restored CD18 expression substantially exceeding this threshold. In addition, we continue to observe a durable treatment effect in the patient followed through one year, with improvement of multiple disease-related skin lesions after therapy and no further requirements for prophylactic anti-infectives.”

Promising results from CIRM-funded projects

Severe Leukocyte Adhesion Deficiency-1 (LAD-1) is a rare condition that causes the immune system to malfunction and reduces its ability to fight off viruses and bacteria. Over time the repeated infections can take a heavy toll on the body and dramatically shorten a person’s life. But now a therapy, developed by Rocket Pharmaceuticals, is showing promise in helping people with this disorder.

The therapy, called RP-L201, targets white blood cells called neutrophils which ordinarily attack and destroy invading particles. In people with LAD-1 their neutrophils are dangerously low. That’s why the new data about this treatment is so encouraging.

In a news release, Jonathan Schwartz, M.D., Chief Medical Officer of Rocket, says early results in the CIRM-funded clinical trial, show great promise:

“Patients with severe LAD-I have neutrophil CD18 expression of less than 2% of normal, with extremely high mortality in early childhood. In this first patient, an increase to 47% CD18 expression sustained over six months demonstrates that RP-L201 has the potential to correct the neutrophil deficiency that is the hallmark of LAD-I. We are also pleased with the continued visible improvement of multiple disease-related skin lesions. The second patient has recently been treated, and we look forward to completing the Phase 1 portion of the registrational trial for this program.”

The results were released at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy.

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These microscopic images show gene expression in muscle stem and progenitor cells as they mature from early development to adulthood (left to right). As part of this process, the cells switch from actively expressing one key gene (green) to another (violet); this is accompanied by the growth of muscle fibers (red).
Photo courtesy: Cell Stem Cell/UCLA Broad Stem Cell Research Center

When you are going on a road-trip you need a map to help you find your way. It’s the same with stem cell research. If you are going to develop a new way to treat devastating muscle diseases, you need to have a map to show you how to build new muscle stem cells. And that’s what researchers at the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCLA – with help from CIRM funding – have done.

The team took muscle progenitor cells – which show what’s happening in development before a baby is born – and compared them to muscle stem cells – which control muscle development after a baby is born. That enabled them to identify which genes are active at what stage of development.

In a news release, April Pyle, senior author of the paper, says this could open the door to new therapies for a variety of conditions:

“Muscle loss due to aging or disease is often the result of dysfunctional muscle stem cells. This map identifies the precise gene networks present in muscle progenitor and stem cells across development, which is essential to developing methods to generate these cells in a dish to treat muscle disorders.”

The study is published in the journal Cell Stem Cell.

Four CIRM Funded Trials Release Results at 2019 ASH Meeting

With more than 17,000 members from nearly 100 countries, the American Society of Hematology (ASH) is an organization composed of clinicians and scientists around the world working to conquer various blood diseases. Currently, they are having their 61st Annual ASH Meeting to highlight some of the exciting work going on in the field. Four of our CIRM funded trials have released promising results at this conference and we wanted to take the opportunity to highlight them below.

Sangamo Therapeutics

Sangamo Therapeutics is conducting a CIRM-funded clinical trial for beta-thalassemia, a severe form of anemia caused by mutations in the hemoglobin gene. The therapy Sangamo is testing takes a patient’s own blood stem cells and, using a gene-editing technology called zinc finger nuclease (ZFN), provides a functional copy of the hemoglobin gene. These modified cells are then given back to the patient. The company announced preliminary results from their first three patients treated. in the clinical trials at the ASH 2019 Conference as well.

Some of the highlights are the following:

  • The first three patients experienced prompt hematopoietic reconstitution, meaning that their supply of blood stem cells was restored.
  • The first three patients experienced no clonal hematopoiesis, meaning that the blood stem cells did not create cells with mutations in the DNA
  • Additional study results are expected in late 2020 once enrollment is complete and all six patients have longer follow-up

You can read more detailed results regarding the first three patients in the press release.

Forty Seven, Inc.

In another CIRM funded trial, Forty Seven, Inc. is testing a treatment for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The treatment involves an antibody called magrolimab in combination with the chemotherapy drug azacitidine. Cancer cells express a signal that send a “don’t eat me” message to white blood cells that are part of the immune system designed to “eat” and destroy unhealthy cells. Magrolimab works by blocking the signal, enabling the body’s own immune system to detect these evasive cancer cells. The goal is to use both magrolimab and azacitidine to make the cancer stem cells vulnerable to being attacked and destroyed by the immune system.

Of the 46 patients evaluated, 24 patients had untreated higher-risk MDS and 22 patients had untreated AML. None of the patients were eligible for treatment with chemotherapy.

In higher-risk MDS, the overall response rate (ORR), which is the proportion of patients in a trial whose tumor is destroyed or significantly reduced by a treatment, was 92%.

Within this group of patients with an ORR, the following was observed:

  • 12 patients (50%) achieved a complete response (CR), meaning that they experienced a disappearance of all signs of cancer in response to treatment.
  • Two patients (8%) achieved hematologic (blood) improvement. 
  • Additionally, two patients (8%) achieved stable disease, meaning the cancer is neither increasing nor decreasing in extent or severity.

In untreated AML, the ORR was 64% and the following was observed within this group patients with an ORR:

  • Nine patients (41%) achieved a CR
  • Three patients (14%) achieved a CR with an incomplete blood count recovery (CRi)
  • One patient (5%) achieved a morphologic leukemia-free state (MLFS), which is defined as the disappearance of all cells with morphologic characteristics of leukemia, accompanied by bone marrow recovery, in response to treatment.
  • Seven patients (32%) achieved stable disease (SD)

The median time to response among MDS and AML patients treated with the combination was 1.9 months.

More details regarding these results are available via the news release.

Oncternal Therapeutics

Onceternal Therapeutics, which is conducting a CIRM-funded trial for a treatment for lymphoma and leukemia, presented results at the 2019 ASH Meeting. The treatment involves an antibody called cirmtuzumab (named after yours truly) being used with a cancer fighting drug called ibrutinib. The antibody recognizes and attaches to a protein on the surface of cancer stem cells. This attachment disables the protein, which slows the growth of the leukemia and makes it more vulnerable to anti-cancer drugs.

Some of the results presented are summarized as follows:

  • Twenty-nine of the 34 patients achieved a response, for an overall best objective response rate of 85%.
  • One patient achieved a complete response (CR) and remained in remission six months after completion of the trial and discontinuation of all anti-CLL therapy. In addition, three patients met radiographic and hematologic response criteria for Clinical CR.
  • Five patients had stable disease.
  • The total clinical benefit rate was 100%.
  • None of the patients died or saw their disease progress.
  • Patients achieved responses rapidly, with 68% of patients achieving a clinical response by three months on the combination therapy.
  • The rise in leukemic cell counts that is typically seen in the first six months with ibrutinib by itself was blunted with the addition of cirmtuzumab, and leukemic cell counts returned toward baseline and normal levels rapidly.

You can read more about these results in the official press release.

Rocket Pharmaceuticals

Last, but not least, Rocket Pharmaceuticals presented results at the 2019 ASH Conference related to a CIRM-funded trial for Leukocyte Adhesion Deficiency-I (LAD-I), a rare pediatric disease caused by a mutation in a specific gene that affects the body’s ability to combat infections. As a result, there is low expression of neutrophil (CD18). The company is testing a treatment that uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient. The goal is to establish functional immune cells, enabling the body to combat infections.  

Here are some of the highlights from the presentation:

  • Initial results from the first pediatric patient treated demonstrate early evidence of safety and potential effectiveness. 
  • The patient exhibited early signs of engraftment
  •  The patient also displayed visible improvement of multiple disease-related skin lesions after receiving therapy
  •  No safety issues related to administration have been identified

More detailed results on this trial are available via the news release.

CIRM Board Approves Funding for New Clinical Trials in Solid Tumors and Pediatric Disease

Dr. Theodore Nowicki, physician in the division of pediatric hematology/oncology at UCLA. Photo courtesy of Milo Mitchell/UCLA Jonsson Comprehensive Cancer Center

The governing Board of the California Institute for Regenerative Medicine (CIRM) awarded two grants totaling $11.15 million to carry out two new clinical trials.  These latest additions bring the total number of CIRM funded clinical trials to 53. 

$6.56 Million was awarded to Rocket Pharmaceuticals, Inc. to conduct a clinical trial for treatment of infants with Leukocyte Adhesion Deficiency-I (LAD-I)

LAD-I is a rare pediatric disease caused a mutation in a specific gene that affects the body’s ability to combat infections.  As a result, infants with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations.  Those that survive infancy experience recurrent severe infections, with mortality rates for severe LAD-I at 60-75% prior to the age of two and survival very rare beyond the age of five.

Rocket Pharmaceuticals, Inc. will test a treatment that uses a patient’s own blood stem cells and inserts a functional version of the gene.  These modified stem cells are then reintroduced back into the patient that would give rise to functional immune cells, thereby enabling the body to combat infections.  

The award is in the form of a CLIN2 grant, with the goal of conducting a clinical trial to assess the safety and effectiveness of this treatment in patients with LAD-I.

This project utilizes a gene therapy approach, similar to that of three other clinical trials funded by CIRM and conducted at UCLA by Dr. Don Kohn, for X-linked Chronic Granulomatous Disease, an inherited immune deficiency “bubble baby” disease known as ADA-SCID, and Sickle Cell Disease.

An additional $4.59 million was awarded to Dr. Theodore Nowicki at UCLA to conduct a clinical trial for treatment of patients with sarcomas and other advanced solid tumors. In 2018 alone, an estimated 13,040 people were diagnosed with soft tissue sarcoma (STS) in the United States, with approximately 5,150 deaths.  Standard of care treatment for sarcomas typically consists of surgery, radiation, and chemotherapy, but patients with late stage or recurring tumor growth have few options.

Dr. Nowicki and his team will genetically modify peripheral blood stem cells (PBSCs) and peripheral blood monocular cells (PBMCs) to target these solid tumors. The gene modified stem cells, which have the ability to self-renew, provide the potential for a durable effect.

This award is also in the form of a CLIN2 grant, with the goal of conducting a clinical trial to assess the safety of this rare solid tumor treatment.

This project will add to CIRM’s portfolio in stem cell approaches for difficult to treat cancers.  A previously funded a clinical trial at UCLA uses this same approach to treat patients with multiple myeloma.  CIRM has also previously funded two clinical trials using different approaches to target other types of solid tumors, one of which was conducted at Stanford and the other at UCLA. Lastly, two additional CIRM funded trials conducted by City of Hope and Poseida Therapeutics, Inc. used modified T cells to treat brain cancer and multiple myeloma, respectively.

“CIRM has funded 23 clinical stage programs utilizing cell and gene medicine approaches” says Maria T. Millan, M.D., the President and CEO of CIRM. “The addition of these two programs, one in immunodeficiency and the other for the treatment of malignancy, broaden the scope of unmet medical need we can impact with cell and gene therapeutic approaches.”