Clinical Trials

How CIRM-funded research is bringing a lifesaving gene therapy to a 5-year-old

/ California Institute for Regenerative Medicine (CIRM) / Leave a comment

For her first year of life, Seersha Sulack stayed mostly in her bedroom because something as simple as a common cold could have killed her. The five-year-old was born with ADA-SCID, a condition so rare that only eight babies a year are born with it in the United States. 

Now, thanks to the work of researchers at UCLA Broad Stem Cell Research Center, a group of dedicated parents at SCID Angels for Life Foundation and funding from California Institute for Regenerative Medicine (CIRM), Seersha is close to receiving a lifesaving gene therapy treatment that will correct the defective gene disabling her immune system. 

Partnering Towards Progress  

Seersha’s journey was recently featured in CNN and is a true testament to the power of partnering to advancing medical research, including for rare diseases. 

“I don’t like the word ‘normal’, but I’m ready to have something normal for her,” her mom told CNN. 

According to the National Institutes of Health (NIH), approximately 7,000 rare diseases affect between 25 and 30 million Americans like Seersha. That equates to 1 in 10 Americans suffering from conditions for which limited treatment options exist. 

“At CIRM we have funded several projects using gene therapy to help treat, and even cure, people with rare diseases such as SCID,” says Dr. Maria T. Millan, the President and CEO of CIRM. “But even an agency with our resources can only do so much.” 

That’s why last year, CIRM signed a Memorandum of Understanding (MOU) with the Foundation for the National Institutes of Health (FNIH) to join the Bespoke Gene Therapy Consortium (BGTC), a public-private partnership managed by FNIH that brings together multiple public and private sector organizations to streamline the development and delivery of gene therapies for rare diseases. 

As part of the Consortium, CIRM will identify specific rare disease gene therapy research programs in California that are eligible to be part of the AMP BGTC. CIRM funding can then support the IND-enabling research, manufacturing and clinical trial activities of these programs. 

“This agreement with the Bespoke Gene Therapy Consortium will enable us to be part of a bigger partnership, one that can advance the field, overcome obstacles and lead to breakthroughs for many rare diseases,” Millan added. 

Investing in Rare Disease Research 

In addition to funding research and clinical trials for prevalent diseases, CIRM recognizes the importance of finding treatments for rare condition such as SCID, retinitis pigmentosa, sickle cell disease, Huntington’s disease, and Duchenne muscular dystrophy.  

Part of our investment in rare diseases includes developing infrastructure programs to promote their access and affordability to diverse communities. That includes launching a Patient Support Program, which will provide resources and financial support to California patients being evaluated or enrolled in CIRM-funded clinical trials, with a particular emphasis on helping underserved populations.  

These efforts will ensure that more patients like Seersha will have access to lifesaving treatments through clinical trials. 

Learn more about CIRM’s commitment to fighting rare conditions like SCID and about our commitment to advancing new therapies for prevalent diseases like cancer, HIV/AIDS and stroke.

Why diversity in clinical trials is essential

/ California Institute for Regenerative Medicine (CIRM) / Leave a comment

The California Institute for Regenerative Medicine (CIRM) is proud to join fellow advocates of clinical trial diversity in applauding a new law that will allow the U.S. Food & Drug Administration (FDA) to require diverse representation in clinical trials. 

A clinical trial, as defined by the FDA, tests potential treatments in human volunteers to see whether they should be approved for wider use in the general population. CIRM has invested in 88 clinical trials to date.

In December 2022, Congress approved a bill that requires diversity action plans for clinical trials used by the FDA. This new law builds on draft guidance issued by the FDA in April 2022 and will move the draft forward to finalization and enforcement.  

The law follows a 2022 report issued by the National Academies of Sciences, Engineering and Medicine that starkly notes:  

“While progress has been made with representation of white women in clinical trials and clinical research, there has been little progress in the last three decades to increase participation of racial and ethnic minority population groups. This underrepresentation is compounding health disparities, with serious consequences for underrepresented groups and for the nation.”  

New Requirements for Clinical Trials

Under the law, clinical trial sponsors will be required to submit a diversity action plan to the FDA along with other important trial documents. The plans, according to the law, should contain:  

  • The sponsor’s goals for clinical study enrollment, disaggregated by age group, sex, and racial and ethnic characteristics.  
  • The rationale for these enrollment goals, including information about the disease or condition and its prevalence or incidence among various demographics.  
  • An explanation of how the sponsor intends to meet the goals, including demographic-specific outreach and enrollment strategies, inclusion and exclusion practices, and diversity training for study personnel. 

A Major Step Forward 

Requiring a clinical trial to expand the representation of diverse people is a major step forward to reverse systemic and structural social inequities in the health care system.  

In a study published in Nature Cell Biology, the authors, which included Dr. Maria Millan, CIRM’s President & CEO, summarized:  

“To address health disparities and facilitate increasingly personalized treatments, we need to develop new models for basic and disease research that reflect diverse ancestral backgrounds and sex and ensure that diverse populations are included among donors and research participants.” 

For example, low participation of Black Americans in clinical trials is well documented including by the JCO Oncology Practice.  The JCO reports that Black Americans constitute at least 13% of the general population in the United States, account for 22% of annual cancer cases, and succumb to prostate, stomach, uterine cancers, and multiple myeloma, at rates twice as high as white people. And yet, Black Americans reflect only 7% of those enrolled in cancer clinical trials.    

Addressing Diversity in Clinical Trials at CIRM 

CIRM requires plans for inclusion of diverse or underserved demographic groups in the clinical trials we fund.  

Proposals for funding (see samples here) must demonstrate an understanding of health disparities associated with the target indication of the study, and plans to:   

  • Include an inclusive group of participations by race, ethnicity, sex, gender, and age.  
  • Address any barriers to trial participation faced by underserved demographic groups.  
  • Guide, as needed, the cultural competency of study researchers.   

“We have incorporated the principles of promoting diversity, equity and inclusion in our research funding programs, education programs and future programs,” Dr. Millan says. “We believe this is essential to ensure that the therapies our support helps advance will reach all patients in need and in particular communities that are disproportionately affected and/or under-served.” 

To learn more about CIRM’s investments in clinical trials, visit this page on our website. To learn more about participating in a clinical trial, click here. 

California agency invests $4 million in stem cell treatment for Parkinson’s Disease

/ Esteban Cortez / 3 Comments

The California Institute for Regenerative Medicine (CIRM) is investing $4 million in a late-stage preclinical project by Ryne Bio aiming to improve treatment for Idiopathic Parkinson’s disease (PD).

PD is characterized by a loss of dopamine producing neurons that result in motor symptoms, such as dyskinesias (involuntary, erratic, writhing movements of the face, arms, legs or trunk) and non-motor effects such as dementia, depression and sleep disorders.

PD is the second-most common neurodegenerative disease after Alzheimer’s disease affecting approximately 1 million people in the U.S. In California, it is estimated that 116,900 people live with PD, representing the highest number of people with the disease in the country.

At its early stages, PD can be treated with medication such as Levodopa to treat symptoms but these become less effective as the disease progresses.

The proposed stem cell therapy in this project offers the potential to restore dopamine neurons, which play a role in many important body functions, including movement and memory.

Investigators at Ryne Bio are aiming to deliver dopamine producing cells to replace the lost neurons to the brain of Parkinson’s disease patients to restore/improve motor function.

The current grant is being funded to conduct Investigational New Drug (IND) enabling, nonclinical safety studies per the US Food and Drug Administration (FDA) Guidance. The IND is the authorization needed to begin a clinical trial in Parkinson’s patients.

CIRM has a vested interest in seeing this therapy succeed. To date, CIRM has invested more than $59 million in helping research for Parkinson’s disease progress from a basic or Discovery level through clinical trials.

Update on SCID patient enrolled in CIRM-funded gene therapy trial

/ Katie Sharify / 2 Comments
Photo credit: UCSF

Hataalii Tiisyatonii Begay (HT) is paving the road for newborns with SCID. When HT was born in 2018 in a remote part of the Navajo nation, he was quickly diagnosed with a rare and -usually fatal- condition. Today, thanks to a therapy developed at UCSF and funded by CIRM, he’s a healthy four-year-old boy running around in cowboy boots.

The California Institute for Regenerative Medicine (CIRM) has invested $12 million to test this therapy in a clinical trial at UC San Francisco.

The disorder is Artemis-SCID, a form of severe combined immunodeficiency disease. Children born with this condition have no functioning immune system so even a simple infection can prove life-threatening or fatal.

Currently, the only approved treatment for Artemis-SCID is a bone-marrow transplant, but many children are unable to find a healthy matched donor for that procedure. Even when they do find a donor, they often need regular injections of antibodies to boost their immune system.

Dr. Morton Cowen and Dr. Jennifer Puck. Photo credit: UCSF

In this clinical trial, UCSF doctors Morton Cowan and Jennifer Puck are using the patient’s own blood stem cells, taken from their bone marrow. In the lab, the cells are modified to correct the genetic mutation that causes Artemis-SCID and then re-infused back into the patients. The goal is that over the course of several months these cells will create a new blood supply, one that is free of Artemis-SCID, and that will in turn help repair the child’s immune system.

In April 2022, HT finally moved back home to Arizona. Nowadays, HT is off his medication and living the life of a normal and happy young child. On the Arizona ranch, there are horses to pet, cattle and sheep to tend, and streams to cool his hands in.

Watch the video below to find out more about HT’s journey and the team at UCSF behind the pioneering trial.

Video courtesy of UCSF

CIRM funds clinical trial to make cancer therapy safer, less toxic

/ Esteban Cortez / 1 Comment

Blood stem cell transplantation following high dose chemotherapy is standard of care and potentially curative for aggressive forms of lymphoma. However, this treatment regimen is limited by severe toxicity and life-threatening complications due to delayed recovery of the blood system and vascular related damage of multiple organs.

Today the governing Board of the California Institute for Regenerative Medicine (CIRM) funded a Phase 3 clinical trial to support development of a safer, more tolerable alternative.

This brings the number of clinical trials funded by CIRM to 86.

The Board awarded $15,000,000 to Dr. Paul Finnegan and Angiocrine Bioscience to test AB-205, human endothelial cells engineered to express a pro-survival factor.

Prior data suggest that, in the setting of chemotherapy and stem cell transplantation, AB-205 cell therapy can accelerate the recovery of the blood system and protects from toxicity by enhancing the recovery from vascular damage. AB-205 is being studied in a Phase 3 trial in adults with lymphoma undergoing high-dose chemotherapy and autologous blood stem cell transplant.

“If successful, this approach can overcome hurdles to the success of chemotherapy and blood stem cell transplantation for the treatment of advanced blood cancer,” says Dr. Maria T. Millan, President and CEO of CIRM. “This Phase 3 trial is the culmination of preclinical research and the initial clinical trial previously funded by CIRM.”

Lymphoma is the most common blood cancer and one of the most common cancers in the United States, accounting for about 4% of all cancers according to the American Cancer Society and the 6th most commonly diagnosed cancer among men and women in California.  It is estimated that there will be 89,010 new cases of lymphoma and 21,170 lymphoma related deaths in the US in 2022 alone.  In California, it is estimated that there will be over 9,250 new cases of lymphoma with over 2,100 deaths.

“Angiocrine Bioscience is honored to be awarded this grant from CIRM to support our AB-205 Phase 3 trial,” commented Angiocrine CEO Dr. Paul Finnegan. “CIRM has been an instrumental partner in our development of AB-205, a novel therapeutic that acts on the patients’ endogenous stem cell niches. The grant award will considerably aid in our effort to bring forth a solution to the unmet need of transplant-related complications.”

Update on spinal cord injury patient enrolled in CIRM-funded stem cell clinical trial

/ Katie Sharify / Leave a comment
Jake Javier and his parents at Duke University

A spinal cord injury (SCI) is devastating, changing a person’s life in an instant. Every year, around the world, between 250,000 and 500,000 people suffer a spinal cord injury. Most of these are caused by trauma to the spinal column, thereby affecting the spinal cord’s ability to send and receive messages from the brain to the body’s systems that control sensory, motor and autonomic function below the level of injury.

Currently, there is nothing that completely reverses SCI damage and most treatment is aimed at rehabilitation and empowering patients to lead as normal a life as possible under the circumstances. Improved treatment options are necessary both to improve patients’ overall quality of life, and to reduce associated healthcare costs.

In 2010, the Geron trial became not only the first clinical trial to be funded by the California Institute for Regenerative Medicine (CIRM), but the first clinical trial in the world using embryonic stem cells.

By 2014, Asterias Biotherapeutics (now Lineage Cell Therapeutics Inc.), acquired the cell therapy assets of Geron and launched its Phase 1/2a clinical trial with the goal of determining the safety of the therapy and the optimal dose of cells to transplant into patients.

In 2016, Jake Javier became the fifth patient to participate in the revived Asterias trial. Regular readers of our blog will remember that Jake is the young man who broke his neck the day before he graduated high school, leaving him paralyzed from the upper chest down.

After enrolling in the CIRM-funded Asterias clinical trial, and receiving a transplant of ten million stem cells, Jake regained enough use of his arms and hands to be able to go to Cal Poly and start his life over.

This video highlights the struggles and challenges he faced in his first year, and his extraordinary spirit in overcoming them.

Video courtesy of Matt Yoon and his team at Cal Poly

Today, Jake is set to graduate from Duke University with his master’s degree in Biomedical Engineering, with plans to help those impacted by neurological injuries or disease.

Watch the video below to learn more about Jake’s personal perspective on his clinical trial participation, the OPC1 clinical study, his future plans and his message to the SCI community.

Video courtesy of Lineage Cell Therapeutics Inc.

Bubble baby treatment cleared to restart clinical trial

/ Kevin McCormack / 1 Comment

Evie Vaccaro: Photo courtesy Nancy Ramos

Three families battling a life-threatening immune disorder got some great news last week. A clinical trial that could save the life of their child has once again been given the go-ahead by the US Food and Drug Administration (FDA).

The clinical trial is the work of UCLA’s Dr. Don Kohn, and was strongly supported by CIRM. It is targeting ADA-SCID, a condition where the child is born without a functioning immune system so even a simple infection could prove fatal. In the past they were called “bubble babies” because some had been placed inside sterile plastic bubbles to protect them from germs.

Dr. Kohn’s approach – using the patient’s own blood stem cells, modified in the lab to correct the genetic mutation that causes the problem – had shown itself to be amazingly effective.  In a study in the prestigious New England Journal of Medicine, the researchers showed that of 50 patients treated all had done well and 97 percent were considered cured.

UCLA licensed the therapy to Orchard Therapeutics, who planned to complete the testing needed to apply for permission to make it more widely available. But Orchard ran into problems and shelved the therapy.

After lengthy negotiations Orchard returned the therapy to UCLA last year and now the FDA has given clearance for UCLA to resume treating patients. That is expected to start early next year using CIRM funds left over when Orchard halted its work.

One of the people who played a big role in helping persuade Orchard to return the therapy to UCLA is Alysia Vaccaro. She is the mother of Evie, a child born with ADA-SCID who was cured by Dr. Kohn and his team and is now a thriving 9 year old.

You can watch an interview we did with Alysia about the impact this research has had on her family, and how important it is for other families with ADA-SCID kids.

Tratando malformaciones congénitas antes del nacimiento 

/ Esteban Cortez / Leave a comment
El bebé, Tobi recibió un tratamiento de células madre, financiado por el CIRM, mientras aún estaba en el útero. To read this blog in English, click here.

Michelle y Jeff se llenaron de felicidad cuando se enteraron de que iban a tener un bebé.  

Luego, un examen de ultrasonido a las 20 semanas del embarazo reveló que el feto tenía espina bífida, una malformación congénita que ocurre cuando la columna vertebral y la médula espinal no se forman de manera adecuada. La espina bífida puede causar parálisis y otras complicaciones serias.   

Se derivó a la pareja a un ensayo clínico en la Universidad de California, Davis, que lleva a cabo la Dra. Diana Farmer, cirujana fetal y neonatal reconocida a nivel internacional, y su colega, el Dr. Aijun Wang.  

En este ensayo clínico, que se basó en una previa investigación financiada por el CIRM, se repara el defecto espinal aplicando células madre de una placenta donada, las cuales se insertan en una estructura sintética y se aplican al defecto de la médula espinal mientras el bebé se encuentra todavía en el útero.   

El hijo de Michelle y Jeff, Tobi, fue el segundo paciente que recibió este tratamiento. Michelle dijo que la cirugía fue difícil, pero el nacimiento de su bebé valió la pena.  

“Cuando lo abrazamos por primera vez dijimos, ‘No puedo creer que hayamos hecho esto. Lo logramos. Lo hicimos sin saber si funcionaría’.”   

A los tres meses, el progreso de Tobi parece promisorio. Jeff y Michelle saben que pueden surgir problemas más adelante, pero por ahora se sienten agradecidos de haber formado parte de este ensayo.

To read this blog in English, click here.

Making transplants easier for kids, and charting a new approach to fighting solid tumors.

/ Kevin McCormack / Leave a comment

Every year California performs around 100 kidney transplants in children but, on average, around 50 of these patients will have their body reject the transplant. These children then have to undergo regular dialysis while waiting for a new organ. Even the successful transplants require a lifetime of immunosuppression medications. These medications can prevent rejection but they also increase the risk of infection, gastrointestinal disease, pancreatitis and cancer.

Dr. Alice Bertaina and her team at Stanford University were awarded $11,998,188 to test an approach that uses combined blood stem cell (HSC) and kidney transplantation with the goal to improve outcomes with kidney transplantation in children. This approach seeks to improve on the blood stem cell preparation through an immune-based purification process.

In this approach, the donor HSC are transplanted into the patient in order to prepare for the acceptance of the donor kidney once transplanted. Donor HSC give rise to cells and conditions that re-train the immune system to accept the kidney. This creates a “tolerance” to the transplanted kidney providing the opportunity to avoid long-term need for medications that suppress the immune system.

Pre-clinical data support the idea that this approach could enable the patient to stop taking any immunosuppression medications within 90 days of the surgery.

Dr. Maria T. Millan, President and CEO of CIRM, a former pediatric transplant surgeon and tolerance researcher states that “developing a way to ensure long-term success of organ transplantation by averting immune rejection while avoiding the side-effects of life-long immunosuppression medications would greatly benefit these children.”

The CIRM Board also awarded $7,141,843 to Dr. Ivan King and Tachyon Therapeutics, Inc to test a drug showing promise in blocking the proliferation of cancer stem cells in solid tumors such as colorectal and gastrointestinal cancer.

Patients with late-stage colorectal cancer are typically given chemotherapy to help stop or slow down the progression of the disease. However, even with this intervention survival rates are low, usually not more than two years.

Tachyon’s medication, called TACH101, is intended to target colorectal cancer (CRC) stem cells as well as the bulk tumor by blocking an enzyme called KDM4, which cancer stem cells need to grow and proliferate.

In the first phase of this trial Dr. King and his team will recruit patients with advanced or metastatic solid tumors to assess the safety of TACH101, and determine what is the safest maximum dose. In the second phase of the trial, patients with gastrointestinal tumors and colorectal cancer will be treated using the dose determined in the first phase, to determine how well the tumors respond to treatment.  

The CIRM Board also awarded $5,999,919 to Dr. Natalia Gomez-Ospina and her team at Stanford University for a late-stage preclinical program targeting Severe Mucopolysaccharidosis type 1, also known as Hurler syndrome. This is an inherited condition caused by a faulty gene. Children with Hurler syndrome lack an enzyme that the body needs to digest sugar. As a result, undigested sugar molecules build up in the body, causing progressive damage to the brain, heart, and other organs. There is no effective treatment and life expectancy for many of these children is only around ten years.

Dr. Gomez-Ospina will use the patient’s own blood stem cells that have been genetically edited to restore the missing enzyme. The goal of this preclinical program is to show the team can manufacture the needed cells, to complete safety studies and to apply to the US Food and Drug Administration for an Investigational New Drug (IND), the authorization needed to begin a clinical trial in people.

Finally the Board awarded $20,401,260 to five programs as part of its Translational program. The goal of the Translational program is to support promising stem cell-based or gene projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use. Those can include therapeutic candidates, diagnostic methods  or devices and novel tools that address critical bottlenecks in research.

The successful applicants are:

APPLICATIONTITLEPRINCIPAL INVESTIGATOR – INSTITUTIONAMOUNT  
TRAN4-14124Cell Villages and Clinical Trial in a Dish with Pooled iPSC-CMs for Drug DiscoveryNikesh Kotecha — Greenstone Biosciences  $1,350,000
TRAN1-14003Specific Targeting Hypoxia Metastatic Breast Tumor with Allogeneic Off-the-Shelf Anti-EGFR CAR NK Cells Expressing an ODD domain of HIF-1αJianhua Yu — Beckman Research Institute of City of Hope  $6,036,002  
TRAN1-13983CRISPR/Cas9-mediated gene editing of Hematopoietic
stem and progenitor cells for Friedreich’s ataxia		Stephanie Cherqui — University of California, San Diego  $4,846,579
TRAN1-13997Development of a Gene Therapy for the Treatment of
Pitt Hopkins Syndrome (PHS) – Translating from Animal Proof of Concept to Support Pre-IND Meeting		Allyson Berent — Mahzi Therapeutics  $4,000,000
TRAN1-13996Overcoming resistance to standard CD19-targeted CAR
T using a novel triple antigen targeted vector		William J Murphy — University of California, Davis  $4,168,679

Neurona Therapeutics Update: First two patients who received treatment experienced significantly less seizures

/ Katie Sharify / Leave a comment

Nearly 3.5 million Americans suffer from some form of epilepsy. It can affect people in different ways from stiff muscles or staring spells, to violent shaking and loss of consciousness.

The impact it has on people’s lives extends far beyond the condition itself. People who suffer from epilepsy experience a higher frequency of depression and other mood disorders, social isolation, challenges in school and with living independently, higher unemployment, limitations on driving, and higher risk of early death.

Medications can help control the seizures in some people, but around one-third of patients don’t respond to those drugs. The alternative is surgery, which is invasive and can cause damage to delicate brain tissue.

Neurona Therapeutics —a clinical stage biotherapeutics company— has developed a therapy called NRTX-1001, which consists of a specialized type of neuronal or brain cell derived from embryonic stem cells. These cells are injected into the brain in the area affected by the seizures where they release a neurotransmitter or chemical messenger that will block the signals in the brain causing the epileptic seizures.

So far, the first two patients treated in the groundbreaking clinical trial—both of whom entered the study with a history of significant monthly seizures that were not controlled by anti-seizure medications—have seen encouraging signs of reduction which suggest that a single dose of NRTX-1001 may have a long-lasting ability to suppress seizures.

The first patient had a 9-year history of seizures and in the six months prior to the administration of NRTX-1001, the patient experienced an average of 32 seizures per month, despite being on several antiepileptic medications. The patient received a single administration of NRTX-1001, the treatment was well tolerated, and there have been no serious or severe adverse events associated with the treatment to date. The patient reported four seizures during the first three months since receiving NRTX-1001.

The second patient treated in the trial also had drug-resistant seizures, with an average of 14 seizures per month in the six months prior to treatment. This individual received NRTX-1001 and in the first week post-treatment had not experienced any serious or severe adverse events, or seizures.

“The early clinical results with NRTX-1001 in epilepsy are very encouraging, and we look forward to enrolling additional patients in the study,” said Dr. Cory Nicholas, Neurona’s president and chief executive officer. “NRTX-1001 is designed to be an off-the-shelf, one-time administration therapy with the potential to durably eliminate seizures and provide a new regenerative cell therapeutic approach in patients for whom anti-seizure medication has failed.”

Dr. Nicholas added, “It has the potential to be disease-modifying without the tissue-destructive procedural risks associated with lobectomy. Further, there are many who are not currently eligible for lobectomy surgery who may be eligible for NRTX-1001 in the future. We are sincerely grateful to everyone involved in the development of NRTX-1001, including the first participants in this pioneering study, their families, and the respective clinical site teams.”

The California Institute for Regenerative Medicine has a vested interest in seeing this therapy succeed. CIRM has invested more than $14 million over four different awards in helping this research progress from a basic or Discovery level through to the current clinical trial.