Stem Cell Agency’s supporting role in advancing research for rare diseases

Orchard

The recent agreement transferring GSK’s rare disease gene therapies to Orchard Therapeutics was good news for both companies and for the patients who are hoping this research could lead to new treatments, even cures, for some rare diseases. It was also good news for CIRM, which played a key role in helping Orchard grow to the point where this deal was possible.

In a news releaseMaria Millan, CIRM’s President & CEO, said:

“At CIRM, our value proposition is centered around our ability to advance the field of regenerative medicine in many different ways. Our funding and partnership has enabled the smooth transfer of Dr. Kohn’s technology from the academic to the industry setting while conducting this important pivotal clinical trial. With our help, Orchard was able to attract more outside investment and now it is able to grow its pipeline utilizing this platform gene therapy approach.”

Under the deal, GSK not only transfers its rare disease gene therapy portfolio to Orchard, it also becomes a shareholder in the company with a 19.9 percent equity stake. GSK is also eligible to receive royalties and commercial milestone payments. This agreement is both a recognition of Orchard’s expertise in this area, and the financial potential of developing treatments for rare conditions.

Dr. Millan says it’s further proof that the agency’s impact on the field of regenerative medicine extends far beyond the funding it offers companies like Orchard.

“Accelerating stem cell therapies to patients with unmet medical needs involves a lot more than just funding research; it involves supporting the research at every stage and creating partnerships to help it fulfill its potential. We invest when others are not ready to take a chance on a promising but early stage project. That early support not only helps the scientists get the data they need to show their work has potential, but it also takes some of the risk out of investments by venture capitalists or larger pharmaceutical companies.”

CIRM’s early support helped UCLA’s Don Kohn, MD, develop a stem cell therapy for severe combined immunodeficiency (SCID). This therapy is now Orchard’s lead program in ADA-SCID, OTL-101.

Sohel Talib, CIRM’s Associate Director Therapeutics and Industry Alliance, says this approach has transformed the lives of dozens of children born with this usually fatal immune disorder.

“This gene correction approach for severe combined immunodeficiency (SCID) has already transformed the lives of dozens of children treated in early trials and CIRM is pleased to be a partner on the confirmatory trial for this transformative treatment for patients born with this fatal immune disorder.”

Dr. Donald B. Kohn UCLA MIMG BSCRC Faculty 180118Dr. Kohn, now a member of Orchard’s scientific advisory board, said:

“CIRM funding has been essential to the overall success of my work, supporting me in navigating the complex regulatory steps of drug development, including interactions with FDA and toxicology studies that enhanced and helped drive the ADA-SCID clinical trial.”

CIRM funding has allowed Orchard Therapeutics to expand its technical operations footprint in California, which now includes facilities in Foster City and Menlo Park, bringing new jobs and generating taxes for the state and local community.

Mark Rothera, Orchard’s President and CEO, commented:

“The partnership with CIRM has been an important catalyst in the continued growth of Orchard Therapeutics as a leading company transforming the lives of patients with rare diseases through innovative gene therapies. The funding and advice from CIRM allowed Orchard to accelerate the development of OTL-101 and to build a manufacturing platform to support our development pipeline which includes 5 clinical and additional preclinical programs for potentially transformative gene therapies”.

Since CIRM was created by the voters of California the Agency has been able to use its support for research to leverage an additional $1.9 billion in funds for California. That money comes in the form of co-funding from companies to support their own projects, partnerships between outside investors or industry groups with CIRM-funded companies to help advance research, and additional funding that companies are able to attract to a project because of CIRM funding.

How CIRM funding creates additional financial support for stem cell research in California

CIRM’s 2017 Annual Report will be going live online very soon. In anticipation of that we are highlighting some of the key elements from the report here on the Stem Cellar.

Two businessman shaking hands

Partnerships that help advance stem cell research

CIRM funds stem cell research.  We all know that.  What you may not know is that CIRM funds also help bring in additional funding and investments to these projects, and as a result, to the state of California.  CIRM’s investment can also be seen as helping validate the credibility of a particular project, taking some of the risk out of investing in it.

We call this second wave of support “Leveraged Funding”. Since we were created in 2004 we have brought in $1.5 billion in Leveraged Funds.

We break that down into three main categories:

  1. Co-Funding– This is funding that was specifically committed to help co-fund a CIRM project. For example, if we fund a for-profit company to do a Phase 1 clinical trial we expect them to co-fund 30% of the cost of the trial. If it’s a Phase 3 clinical trial the co-funding amount rises to 50%.  To date we have received $911 million in co-funding.
  2. Partnership Funding– Partnership Funding – This is non-CIRM funding committed by partners, not already captured by Co-Funding. For example, our Board’s decision to invest in a project can sometimes be seen as a kind of “Good Housekeeping Seal of Approval” because it shows this project has been reviewed by experts and recommended for funding.  Our funding allows investigators to do the early work and get data that helps attract funding from outside investors. These funds can be committed or spent at the same time as CIRM funds or to further the project after the CIRM award expires. Since 2004, we have helped generate $528 million in partnership funding.
  3. Additional Leverage– This is everything not covered by the first two categories but is mainly non-CIRM funding reported in the “Outcomes Survey”, which the lead investigator on the project completes at the end of the award. This lets us know about any non-CIRM funding they received as a result of their CIRM project (such as money from the National Institutes of Health or other agency grants). More than $395 million in additional leverage funding has been raised because of CIRM.

In 2017, we saw eight projects that we support attract additional support, almost $390 million, from outside investors.

  Disease Area  Industry Partner 2017 Funding
1. Adenosine deaminase-deficient Severe Combined Immunodeficiency Orchard Therapeutics $110,000,000
2. X-Linked Chronic Granulomatous Disease Orchard Therapeutics Not disclosed
3. Acute Myeloid Leukemia Forty Seven, Inc. $75,000,000
4. Pediatrics Genetic Disorder AVROBIO, Inc. Not disclosed
5. HIV/AIDS CSL Behring $91,000,000
6. Chronic Lymphocytic Leukemia Oncternal, Inc. $18,400,000
7. Brain Cancer Mustang Bio, Inc. $94,500,000
8. Age-related Macular Degeneration Santen Pharmaceutical Not disclosed
  Total   $388,900,000

Our goal is to do all we can to support the best science and move it out of the lab and into clinical trials in people. Obviously, providing funding is a key step, but it’s far from the only step. For us, it’s really just the first step.

On Wednesday, we’ll profile one of the CIRM-funded researchers whose work is attracting support from outside investors, work that is taking a whole new approach to fighting a deadly brain cancer.

Progress to a Cure for Bubble Baby Disease

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded clinical trials for the treatment of a devastating, usually fatal, primary immune disease that strikes newborn babies.

evangelina in a bubble

Evie, a former “bubble baby” enjoying life by playing inside a giant plastic bubble

‘Bubble baby disease’ will one day be a thing of the past. That’s a bold statement, but I say it with confidence because of the recent advancements in stem cell gene therapies that are curing infants of this life-threatening immune disease.

The scientific name for ‘bubble baby disease’ is severe combined immunodeficiency (SCID). It prevents the proper development of important immune cells called B and T cells, leaving newborns without a functioning immune system. Because of this, SCID babies are highly susceptible to deadly infections, and without treatment, most of these babies do not live past their first year. Even a simple cold virus can be fatal.

Scientists are working hard to develop stem cell-based gene therapies that will cure SCID babies in their first months of life before they succumb to infections. The technology involves taking blood stem cells from a patient’s bone marrow and genetically correcting the SCID mutation in the DNA of these cells. The corrected stem cells are then transplanted back into the patient where they can grow and regenerate a healthy immune system. Early-stage clinical trials testing these stem cell gene therapies are showing very encouraging results. We’ll share a few of these stories with you below.

CIRM-funded trials for SCID

CIRM is funding three clinical trials, one from UCLA, one at Stanford and one from UCSF & St. Jude Children’s Research Hospital, that are treating different forms of SCID using stem cell gene therapies.

Adenosine Deaminase-Deficient SCID

The first trial is targeting a form of the disease called adenosine deaminase-deficient SCID or ADA-SCID. Patients with ADA-SCID are unable to make an enzyme that is essential for the function of infection-fighting immune cells called lymphocytes. Without working lymphocytes, infants eventually are diagnosed with SCID at 6 months. ADA-SCID occurs in approximately 1 in 200,000 newborns and makes up 15% of SCID cases.

CIRM is funding a Phase 2 trial for ADA-SCID that is testing a stem cell gene therapy called OTL-101 developed by Dr. Don Kohn and his team at UCLA and a company called Orchard Therapeutics. 10 patients were treated in the trial, and amazingly, nine of these patients were cured of their disease. The 10th patient was a teenager who received the treatment knowing that it might not work as it does in infants. You can read more about this trial in our blog from earlier this year.

In a recent news release, Orchard Therapeutics announced that the US Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation to OTL-101, meaning that the company will qualify for priority review for drug approval by the FDA. You can read more about what this designation means in this blog.

X-linked SCID

The second SCID trial CIRM is funding is treating patients with X-linked SCID. These patients have a genetic mutation on a gene located on the X-chromosome that causes the disease. Because of this, the disease usually affects boys who have inherited the mutation from their mothers. X-linked SCID is the most common form of SCID and appears in 1 in 60,000 infants.

UCSF and St. Jude Children’s Research Hospital are conducting a Phase 1/2 trial for X-linked SCID. The trial, led by Dr. Brian Sorrentino, is transplanting a patient’s own genetically modified blood stem cells back into their body to give them a healthy new immune system. Patients do receive chemotherapy to remove their diseased bone marrow, but doctors at UCSF are optimizing low doses of chemotherapy for each patient to minimize any long-term effects. According to a UCSF news release, the trial is planning to treat 15 children over the next five years. Some of these patients have already been treated and we will likely get updates on their progress next year.

CIRM is also funding a third clinical trial out of Stanford University that is hoping to make bone marrow transplants safer for X-linked SCID patients. The team, led by Dr. Judy Shizuru, is developing a therapy that will remove unhealthy blood stem cells from SCID patients to improve the survival and engraftment of healthy bone marrow transplants. You can read more about this trial on our clinical trials page.

SCID Patients Cured by Stem Cells

These clinical trial results are definitely exciting, but what is more exciting are the patient stories that we have to share. We’ve spoken with a few of the families whose children participated in the UCLA and UCSF/St. Jude trials, and we asked them to share their stories so that other families can know that there is hope. They are truly inspiring stories of heartbreak and joyful celebration.

Evie is a now six-year-old girl who was diagnosed with ADA-SCID when she was just a few months old. She is now cured thanks to Don Kohn and the UCLA trial. Her mom gave a very moving presentation about Evie’s journey at the CIRM Bridges Trainee Annual Meeting this past July.  You can watch the 20-minute talk below:

Ronnie’s story

Ronnie SCID kid

Ronnie: Photo courtesy Pawash Priyank

Ronnie, who is still less than a year old, was diagnosed with X-linked SCID just days after he was born. Luckily doctors told his parents about the UCSF/St. Jude trial and Ronnie was given the life-saving stem cell gene therapy before he was six months old. Now Ronnie is building a healthy immune system and is doing well back at home with his family. Ronnie’s dad Pawash shared his families moving story at our September Board meeting and you can watch it here.

Our mission at CIRM is to accelerate stem cell treatments to patients with unmet medical needs. We hope that by funding promising clinical trials like the ones mentioned in this blog, that one day soon there will be approved stem cell therapies for patients with SCID and other life-threatening diseases.

CIRM-funded life-saving stem cell therapy gets nod of approval from FDA

Cured_AR_2016_coverIf you have read our 2016 Annual Report (and if you haven’t you should, it’s brilliant) or just seen the cover you’ll know that it features very prominently a young girl named Evie Padilla Vaccaro.

Evie was born with Severe Combined Immunodeficiency or SCID – also known as “bubble baby disease”; we’ve written about it here. SCID is a rare but deadly immune disorder which leaves children unable to fight off simple infections. Many children with SCID die in the first few years of life.

Fortunately for Evie and her family, Dr. Don Kohn and his team at UCLA, working with a UK-based company called Orchard Therapeutics Ltd., have developed a treatment called OTL-101. This involves taking the patient’s own blood stem cells, genetically modifying them to correct the SCID mutation, and then returning the cells to the patient. Those modified cells create a new blood supply, and repair the child’s immune system.

Evie was treated with OTL-101 when she was a few months old. She is cured. And she isn’t the only one. To date more than 40 children have been treated with this method. All have survived and are doing well.

Orchard Therapeutics

 FDA acknowledgement

Because of that success the US Food and Drug Administration (FDA) has granted OTL-101 Rare Pediatric Disease Designation. This status is given to a treatment that targets a serious or life-threatening disease that affects less than 200,000 people, most of whom are under 18 years of age.

The importance of the Rare Pediatric Disease Designation is that it gives the company certain incentives for the therapy’s development, including priority review by the FDA. That means if it continues to show it is safe and effective it may have a faster route to being made more widely available to children in need.

In a news release Anne Dupraz, PhD, Orchard’s Chief Regulatory Officer, welcomed the decision:

“Together with Orphan Drug and Breakthrough Therapy Designations, this additional designation is another important development step for the OTL-101 clinical program. It reflects the potential of this gene therapy treatment to address the significant unmet medical need of children with ADA-SCID and eligibility for a Pediatric Disease Priority Review voucher at time of approval.”

Creating a trend

This is the second time in less than two weeks that a CIRM-funded therapy has been awarded Rare Pediatric Disease designation. Earlier this month Capricor Therapeutics was given that status for its treatment for Duchenne Muscular Dystrophy.

Two other CIRM-funded clinical trials – Humacyte and jCyte – have been given Regenerative Medicine Advanced Therapy Designation (RMAT) by the FDA. This makes them eligible for earlier and faster interactions with the FDA, and also means they may be able to apply for priority review and faster approval.

All these are encouraging signs for a couple of reasons. It suggests that the therapies are showing real promise in clinical trials. And it shows that the FDA is taking steps to encourage those therapies to advance as quickly – and safely of course – as possible.

Credit where credit is due

In the past we have been actively critical of the FDA’s sluggish pace in moving stem cell therapies out of the lab and into clinical trials where they can be tested in people. So when the FDA does show signs of changing the way it works it’s appropriate that that we are actively supportive.

Getting these designations is, of course, no guarantee the therapies will ultimately prove to be successful. But if they are, creating faster pathways means they can get to patients, the people who really need them, at a much faster pace.