Graphite Bio launches and will prepare for clinical trial based on CIRM-funded research

Josh Lehrer, M.D., CEO of Graphite Bio

This week saw the launch of the 45th startup company enabled by CIRM funding of translational research at California academic institutions. Graphite Bio officially launched with the help of $45M in funding led by bay area venture firms Versant Ventures and Samsara BioCapital to spinout a novel CRISPR gene editing platform from Stanford University to treat severe diseases. Graphite Bio’s lead candidate is for sickle cell disease and it harnesses CRISPR gene correction technology to correct the single DNA mutation in sickle cell disease and to restore normal hemoglobin expression in the red blood cells of sickle cell patients (Learn more about CRISPR from a previous blog post linked here).

Matt Porteus, M.D., Ph.D (left) and Maria Grazia Roncarolo, M.D. (right)
Graphite Bio scientific founders

Matt Porteus, M.D., Ph.D and Maria Grazia Roncarolo, M.D., both from Stanford University, are the company’s scientific founders. Dr. Porteus, Dr. Roncarolo, and the Stanford team are currently supported by a CIRM  late stage preclinical grant  to complete the final preclinical studies and to file an Investigational New Drug application with the FDA, which will enable Graphite Bio to commence clinical studies of the CRISPR sickle cell disease gene therapy candidate in sickle cell patients in 2021.

Josh Lehrer, M.D., was appointed CEO of Graphite Bio and elaborated on the company’s gene editing approach in a news release.

“Our flexible, site-specific approach is extremely powerful and could be used to definitively correct the underlying causes of many severe genetic diseases, and also is applicable to broader disease areas. With backing from Versant and Samsara, we look forward to progressing our novel medicines into the clinic for patients with high unmet needs.”

In a press release, Dr. Porteus take a retrospective look on his preclinical research and its progress towards a clinical trial.

“It is gratifying to see our work on new gene editing approaches being translated into novel therapies. I’m very excited to be working with Versant again on a start-up and I look forward to collaborating with Samsara and the Graphite Bio team to bring a new generation of genetic treatments to patients.”

CIRM’s funding of late stage preclinical projects such this one is critical to its funding model, which de-risks the discovery, translational development and clinical proof of concept of innovative stem cell-based treatments until they can attract industry partnerships. You can learn more about CIRM-enabled spinout companies and CIRM’s broader effort to facilitate industry partnering for its portfolio projects on CIRM’s Industry Alliance Program website.

You can contact CIRM’s Director of Business Development at the email below to learn more about the Industry Alliance Program.

Shyam Patel, Ph.D.
Director, Business Development
Email: spatel@cirm.ca.gov

CIRM Board Expands COVID-19 Efforts

Coronavirus particles, illustration. Courtesy KTSDesign/Science Photo Library

This past Friday, the governing Board of the California Institute for Regenerative Medicine (CIRM) expanded the eligibility criteria for COVID-19 related projects to develop new treatments against the virus.  Just two weeks ago, the Board approved $5 million in emergency funding for COVID-19 research.

One major addition is allowing research related to convalescent plasma to be eligible for CIRM COVID-19 emergency funding.  Plasma is a component of blood that carries cells and antibodies.  Blood plasma from patients that have recovered from COVID-19, referred to as convalescent plasma, contains antibodies against the virus and could be used as a potential treatment for COVID-19 patients.

In addition to this, potential clinical studies of convalescent plasma are now approved for use by the U.S. Food and Drug Administration (FDA) single-patient emergency Investigational New Drug (eIND) pathway as opposed to only a traditional IND.  Before treatments can be tested in humans, a traditional IND needs to be filed.  In an emergency situation such as the coronavirus pandemic, an eIND can be filed to begin testing the treatment faster.

In order to address the disproportionate impact of COVID-19 on underserved communities, priority will be given to projects that directly address these disparities. 

Lastly, potential clinical programs for COVID-19 are now approved to start incurring allowable project costs, at risk, from the date of the application submission deadline.  This would give researchers the opportunity to start their projects earlier and cover project costs retroactively if they are approved for funding.

“The intent behind this amendment is to be responsive to this COVID-19 crisis by leveraging CIRM’s funding programs, processes, and infrastructure within the scientific ecosystem that it has supported to date,” said Maria T. Millan, M.D., President and CEO of CIRM. “By providing an opportunity for the medical and scientific community to gather important data while using convalescent plasma treatment protocols on an emergency basis, CIRM is joining the global effort to expedite treatments to patients in need in the midst of this global pandemic.”

CIRM has established an open call for proposals and will accept applications on a bi-monthly basis.

Please refer to the following Program Announcement for more details:

·      Special Call for COVID-19 Projects

To Submit an Application:

  1. Go to the Grants Management Portal (https://grants.cirm.ca.gov) and log in with your existing CIRM Username and Password. If you do not have a Username, Click on the “New User” link and follow the instructions to create a CIRM Username and password.
  2. After logging in, click on the Menu tab. Select the tab labeled “Open Programs“. Under the section labeled “RFAs and Programs Open for Applications“, click on the “Start a Grant Application” link for your selected program.
  3. Complete each section of the Application by clicking on the appropriate link and following the posted instructions. Proposal templates can be located and submitted under the “Uploads” section.
  4. To submit your Application, click on the “Done with Application” button. The “Done with Application” button will be enabled when all of the mandatory sections have been completed. Please note that once this has been selected, you will no longer be able to make changes to your Application.
  5. To confirm submission of your Application, select the tab labeled “Your Applications” and check the table under the section labeled “Your Submitted Applications“. You will see your Application number and project title listed once the submission process has been completed.

From bench to bedside – CIRM plays a vital role in accelerating science

Dr. Maria T. Millan, President & CEO of CIRM

The field of stem cell research and regenerative medicine has exploded in the last few years with new approaches to treat a wide array of diseases. Although these therapies are quite promising, they face many challenges in trying to bring them from the laboratory and into patients. But why is this? What can we do to ensure that these approaches are able to cross the finish line?

A new article published in Cell Stem Cell titled Translating Science into the Clinic: The Role of Funding Agencies takes a deeper dive into these questions and how agencies like CIRM play an active role in helping advance the science. The article was written by Dr. Maria T. Millan, President & CEO of CIRM, and Dr. Gil Sambrano, Vice President of Portfolio Development and Review at CIRM.

Although funding plays an essential role in accelerating science, it is not by itself sufficient. The article describes how CIRM has established internal processes and procedures that aim to help accelerate projects in the race to the finish line. We are going to highlight a few of these in this post, but you can read about them in full by clicking on the article link here.

One example of accelerating the most promising projects was making sure that they make important steps along the way. For potential translational awards, which “translate” basic research into clinical trials, this means having existing data to support a therapeutic approach. For pre-clinical and clinical awards, it means meeting with the Food and Drug Administration (FDA) and having an active investigational new drug (IND) approved or pre-IND, important steps that need to be taken before these treatments can be tested in humans. Both of these measures are meant to ensure that the award is successful and progress quickly.

Another important example is not just giving these projects the funding in its entirety upfront, rather, tying it to milestones that guide a project to successful completion. Through this process, projects funded by CIRM become focused on achieving clear measurable objectives, and activities that detract from those goals are not supported.

Aside from requirements and milestones tied to funding, there are other ways that CIRM helps bolster its projects.

One of these is an outreach project CIRM has implemented that identifies investigators and projects with the potential to enhance already existing projects. This increases the number of people applying to CIRM projects as well as the quality of the applications.

Another example is CIRM’s Industry Alliance Program, which facilitates partnerships between promising CIRM-funded projects and companies capable of bringing an approved therapy to market. The ultimate goal is to have therapies become available to patients, which is generally made possible through commercialization of a therapeutic product by a pharmaceutical or biotechnology company.

CIRM has also established advisory panels for its clinical and translational projects, referred to as CAPs and TAPs. They are composed of external scientific advisors with expertise that complements the project team, patient advocate advisors, and CIRM Science Officers. The advisory panel provides guidance and brings together all available resources to maximize the likelihood of achieving the project objective on an accelerated timeline.

Lastly, and most importantly, CIRM has included patient advocates and patient voices in the process to help keep the focus on patient needs. In order to accelerate therapies to the clinic, funders and scientists need input on what ultimately matters to patients. Investing effort and money on potential therapies that will have little value to patients is a delay on work that really matters. Even if there is not a cure for some of these diseases, making a significant improvement in quality of life could make a big difference to patients. There is no substitute to hearing directly from patients to understand their needs and to assess the balance of risk versus benefit. As much as science drives the process of bringing these therapies to light, patients ultimately determine its relevance.

Turning the corner with the FDA and NIH; CIRM creates new collaborations to advance stem cell research

FDAThis blog is part of the Month of CIRM series on the Stem Cellar

A lot can change in a couple of years. Just take our relationship with the US Food and Drug Administration (FDA).

When we were putting together our Strategic Plan in 2015 we did a survey of key players and stakeholders at CIRM – Board members, researchers, patient advocates etc. – and a whopping 70 percent of them listed the FDA as the biggest impediment for the development of stem cell treatments.

As one stakeholder told us at the time:

“Is perfect becoming the enemy of better? One recent treatment touted by the FDA as a regulatory success had such a high clinical development hurdle placed on it that by the time it was finally approved the standard of care had evolved. When it was finally approved, five years later, its market potential had significantly eroded and the product failed commercially.”

Changing the conversation

To overcome these hurdles we set a goal of changing the regulatory landscape, finding a way to make the system faster and more efficient, but without reducing the emphasis on the safety of patients. One of the ways we did this was by launching our “Stem Cell Champions” campaign to engage patients, patient advocates, the public and everyone else who supports stem cell research to press for change at the FDA. We also worked with other organizations to help get the 21st Century Cures Act passed.

21 century cures

Today the regulatory landscape looks quite different than it did just a few years ago. Thanks to the 21st Century Cures Act the FDA has created expedited pathways for stem cell therapies that show promise. One of those is called the Regenerative Medicine Advanced Therapy (RMAT) designation, which gives projects that show they are both safe and effective in early-stage clinical trials the possibility of an accelerated review by the FDA. Of the first projects given RMAT designation, three were CIRM-funded projects (Humacyte, jCyte and Asterias)

Partnering with the NIH

Our work has also paved the way for a closer relationship with the National Institutes of Health (NIH), which is looking at CIRM as a model for advancing the field of regenerative medicine.

In recent years we have created a number of innovations including introducing CIRM 2.0, which dramatically improved our ability to fund the most promising research, making it faster, easier and more predictable for researchers to apply. We also created the Stem Cell Center  to make it easier to move the most promising research out of the lab and into clinical trials, and to give researchers the support they need to help make those trials successful. To address the need for high-quality stem cell clinical trials we created the CIRM Alpha Stem Cell Clinic Network. This is a network of leading medical centers around the state that specialize in delivering stem cell therapies, sharing best practices and creating new ways of making it as easy as possible for patients to get the care they need.

The NIH looked at these innovations and liked them. So much so they invited CIRM to come to Washington DC and talk about them. It was a great opportunity so, of course, we said yes. We expected them to carve out a few hours for us to chat. Instead they blocked out a day and a half and brought in the heads of their different divisions to hear what we had to say.

A model for the future

We hope the meeting is, to paraphrase Humphrey Bogart at the end of Casablanca, “the start of a beautiful friendship.” We are already seeing signs that it’s not just a passing whim. In July the NIH held a workshop that focused on what will it take to make genome editing technologies, like CRISPR, a clinical reality. Francis Collins, NIH Director, invited CIRM to be part of the workshop that included thought leaders from academia, industry and patients advocates. The workshop ended with a recommendation that the NIH should consider building a center of excellence in gene editing and transplantation, based on the CIRM model (my emphasis).  This would bring together a multidisciplinary disease team including, process development, cGMP manufacturing, regulatory and clinical development for Investigational New Drug (IND) filing and conducting clinical trials, all under one roof.

dr_collins

Dr. Francis Collins, Director of the NIH

In preparation, the NIH visited the CIRM-funded Stem Cell Center at the City of Hope to explore ways to develop this collaboration. And the NIH has already begun implementing these suggestions starting with a treatment targeting sickle cell disease.

There are no guarantees in science. But we know that if you spend all your time banging your head against a door all you get is a headache. Today it feels like the FDA has opened the door and that, together with the NIH, they are more open to collaborating with organizations like CIRM. We have removed the headache, and created the possibility that by working together we truly can accelerate stem cell research and deliver the therapies that so many patients desperately need.

 

 

 

 

 

 

A ‘Call to Action’ for change at the FDA

hd

It’s bad enough to have to battle a debilitating and ultimately deadly disease like Huntington’s disease (HD). But it becomes doubly difficult and frustrating when you feel that the best efforts to develop a therapy for HD are running into a brick wall.

That’s how patients and patient advocates working on HD feel as they see the Food and Drug Administration (FDA) throw up what they feel are unnecessary obstacles in the way of promising research.

So the group Help 4HD International has decided to push back, launching an online campaign to get its supporters to pressure the FDA into taking action. Any action.

Posing the question “Does the FDA understand that time is something we simply don’t have?” Help 4HD is urging people to write to the FDA:

“We have heard the FDA say they feel like our loved ones have quality of life at the end stages of HD. We have heard them say people with HD get to live for 20 years after diagnosis. It seems like the FDA doesn’t understand what we are having to live with generation after generation. We have seen HD research die because the researcher couldn’t get an IND (Investigational New Drug, or approval to put a new drug into clinical trials) from the FDA. We have seen trials that should be happening here in the USA move to other countries because of this. We have seen the FDA continue to put up delays and roadblocks. We are lucky to have amazing research going on for HD/JHD (juvenile HD) right now, but what is that research worth if the FDA doesn’t let it go into clinical trials? Drug development is a business and costs millions of dollars. If the FDA continues to refuse INDs, the fear is that companies will stop investing in HD research. This is a fate that we can’t let happen! We need to write to the FDA and let them know our frustrations and also help them understand our disease better.”

The group has drafted a sample letter for people to use or adapt as they see fit. They’ve even provided them with the address to mail the letter to. In short, they are making it as easy as possible to get as many people as possible to write to the FDA and ask for help.

The HD community is certainly not the only one frustrated at the FDA’s  glacial pace of approval of for clinical trials. That frustration is one of many reasons why Congress passed the 21st Century Cures Act late last year. That’s also the reason why we started our Stem Cell Champions campaign, to get the FDA to create a more efficient, but no less safe, approval process.

Several of our most active Stem Cell Champions – like Frances Saldana, Judy Roberson and Katie Jackson – are members of the HD Community. Last May several members of the CIRM Team attended the HD-Care Conference, held to raise awareness about the unmet medical needs of this community. We blogged about it here.

While this call to action comes from the HD community it may serve as a template for other organizations and communities. Many have the same frustrations at the slow pace of approval of therapies for clinical trials.

We are hoping the 21st Century Cures Act will lead to the desired changes at the FDA. But until we see proof that’s the case we understand and support the sense of urgency that the HD community has. They don’t have the luxury of time.

 

 

Creating a “Pitching Machine” to speed up our delivery of stem cell treatments to patients

hitting-machine

When baseball players are trying to improve their hitting they’ll use a pitching machine to help them fine tune their stroke. Having a device that delivers a ball at a consistent speed can help a batter be more consistent and effective in their swing, and hopefully get more hits.

That’s what we are hoping our new Translating and Accelerating Centers will do. We call these our “Pitching Machine”, because we hope they’ll help researchers be better prepared when they apply to the Food and Drug Administration (FDA) for approval to start a clinical trial, and be more efficient and effective in the way they set up and run that clinical trial once they get approval.

The CIRM Board approved the Accelerating Center earlier this summer. The $15 million award went to QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider.

The Accelerating Center will provide key core services for researchers who have been given approval to run a clinical trial, including:

  • Regulatory support and management services
  • Clinical trial operations and management services
  • Data management, biostatistical and analytical services

The reason why these kinds of service are needed is simple, as Randy Mills, our President and CEO explained at the time:

“Many scientists are brilliant researchers but have little experience or expertise in navigating the regulatory process; this Accelerating Center means they don’t have to develop those skills; we provide them for them.”

The Translating Center is the second part of the “Pitching Machine”. That is due to go to our Board for a vote tomorrow. This is an innovative new center that will support the stem cell research, manufacturing, preclinical safety testing, and other activities needed to successfully apply to the FDA for approval to start a clinical trial.

The Translating Center will:

  • Provide consultation and guidance to researchers about the translational process for their stem cell product.
  • Initiate, plan, track, and coordinate activities necessary for preclinical Investigational New Drug (IND)-enabling development projects.
  • Conduct preclinical research activities, including pivotal pharmacology and toxicology studies.
  • Manufacture stem cell and gene modified stem cell products under the highest quality standards for use in preclinical and clinical studies.

The two centers will work together, helping researchers create a comprehensive development plan for every aspect of their project.

For the researchers this is important in giving them the support they need. For the FDA it could also be useful in ensuring that the applications they get from CIRM-funded projects are consistent, high quality and meet all their requirements.

We want to do everything we can to ensure that when a CIRM-funded therapy is ready to start a clinical trial that its application is more likely to be a hit with the FDA, and not to strike out.

Just as batting practice is crucial to improving performance in baseball, we are hoping our “Pitching Machine” will raise our game to the next level, and enable us to deliver some game-changing treatments to patients with unmet medical needs.

 

Doing nothing is not OK: A call for change at the FDA

FDA-NotApprovedStampThe US Food and Drug Administration (FDA) is caught between a rock and a hard place. And CIRM is going to try and help them get out from under that.

As things stand today, if the FDA approves a therapy quickly and a patient later dies from it, then they are widely criticized. If they take a long time to approve a therapy and people die waiting for that treatment, then they are just as widely criticized.

So maybe it’s time to help them change that, by creating a new pathway that allows for a faster, more efficient, but equally safe, process of approving stem cell therapies.

This was a topic that CIRM’s President and CEO, Dr. Randy Mills, took on at last week’s World Stem Cell Summit. He highlighted our mission – accelerating stem cell therapies to patients with unmet medical needs – as the driving force behind everything we do, including regulatory reform:

“We have had the current FDA regulatory structure for cell therapy in place for 15 years, and in that 15 years not one stem cell therapy has been approved. The scoreboard is not lying, there’s a zero on it. Not one therapy has been approved. There is an issue here, we can’t ignore that fact and so we made it part of our proposed new Strategic Plan to try and remove this burden.

“There is an excessively long translational pathway to get an Investigational New Drug (IND) approval from the FDA (a necessary step to proceed with testing a therapy in a clinical trial). For non-cell therapies it takes 3-4 years to get an IND. For cell therapies it takes 6-8 years, twice as long.”

Mills says many potential therapies have been abandoned, or even stopped before they even got started, simply because the regulatory hurdles are so many and the costs so high.

“We are not anti-regulation, we are not anti-FDA, and we are not calling for the removal of rules and regulations around stem cell therapies, that would be bad for patients and research. These therapies have risks and we are not proposing any strategy that puts things on the market without any testing or safety data. But right now we are being so careful about safety to ensure patients are not put at risk while those same patients are dying from their disease.”

Chaohong Fan, MD, PhD, a Medical Officer at the FDA was in the audience and said the people at the FDA really want to help, that they feel it’s part of their mission.

Mills said he had no doubts that the people at the FDA are committed and passionate about what they do. He says it’s not that people at the FDA aren’t working, it’s that the process isn’t working, and needs to be transformed.

“At CIRM we are saying doing nothing is not OK. It’s not OK. So we are going to be working with patients and patient advocates, companies, researchers and the FDA to make change, to make it easier for patients to get access to the therapies they need.”