A model for success

Dr. Maria Millan, CIRM’s President & CEO

Funding models are rarely talked about in excited tones.  It’s normally relegated to the dry tomes of academia. But in CIRM’s case, the funding model we have created is not just fundamental to our success in advancing regenerative medicine in California, it’s also proving to be a model that many other agencies are looking at to see if they can replicate it.

A recent article in the journal Cell & Gene Therapy Insights looks at what the CIRM model does and how it has achieved something rather extraordinary.

Full disclosure. I might be a tad biased here as the article was written by my boss, Dr. Maria Millan, and two of my colleagues, Dr. Sohel Talib and Dr. Shyam Patel.

I won’t go into huge detail here (you can get that by reading the article itself) But the article “highlights 3 elements of CIRM’s funding model that have enabled California academic researchers and companies to de-risk development of novel regenerative medicine therapies and attract biopharma industry support.”

Those three elements are:

1. Ensuring that funding mechanisms bridge the entire translational “Valley of Death”

2. Constantly optimizing funding models to meet the needs of a rapidly evolving industry

3. Championing the portfolio and proactively engaging potential industry partners

As an example of the first, they point to our Disease Team awards. These were four-year investments that gave researchers with promising projects the time, support and funds they needed to not only develop a therapy, but also move it out of academia into a company and into patients.  Many of these projects had struggled to get outside investment until CIRM stepped forward. One example they offer is this one.

“CIRM Disease Team award funding also enabled Dr. Irving Weissman and the Stanford University team to discover, develop and obtain first-in-human clinical data for the innovative anti-CD47 antibody immunotherapy approach to cancer. The spin-out, Forty Seven, Inc., then leveraged CIRM funding as well as venture and public market financing to progress clinical development of the lead candidate until its acquisition by Gilead Sciences in April 2020 for $4.9B.”

But as the field evolved it became clear CIRM’s funding model had to evolve too, to better meet the needs of a rapidly advancing industry. So, in 2015 we changed the way we worked. For example, with clinical trial stage projects we reduced the average time from application to funding from 22 months to 120 days. In addition to that applications for new clinical stage projects were able to be submitted year-round instead of only once or twice a year as in the past.

We also created hard and fast milestones for all programs to reach. If they met their milestone funding continued. If they didn’t, funding stopped. And we required clinical trial stage projects, and those for earlier stage for-profit companies, to put up money of their own. We wanted to ensure they had “skin in the game” and were as committed to the success of their project as we were.

Finally, to champion the portfolio we created our Industry Alliance Program. It’s a kind of dating program for the researchers CIRM funds and companies looking to invest in promising projects. Industry partners get a chance to look at our portfolio and pick out projects they think are interesting. We then make the introductions and see if we can make a match.

And we have.

“To date, the IAP has also formally enrolled 8 partners with demonstrated commitment to cell and gene therapy development. The enrolled IAP partners represent companies both small and large, multi-national venture firms and innovative accelerators.

Over the past 18 months, the IAP program has enabled over 50 one-on-one partnership interactions across CIRM’s portfolio from discovery stage pluripotent stem cell therapies to clinical stage engineered HSC therapies.”

As the field continues to mature there are new problems emerging, such as the need to create greater manufacturing capacity to meet the growth in demand for high quality stem cell products. CIRM, like all other agencies, will also have to evolve and adapt to these new demands. But we feel with the model we have created, and the flexibility we have to pivot when needed, we are perfectly situated to do just that.

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 Highlights Industrial Alliance Program (IAP)

In the addition to the innovative scientists and clinicians who conceive and develop novel experimental therapies, it takes a village to drive a promising experimental therapy through phases of clinical trials, regulatory marketing approval, and commercialization before it becomes broadly accessible to patients with unmet medical needs. In this case, the village is the broader industry including institutional investors and biopharma companies that have the capital, resources and expertise to carry the development programs past the finish line. 

A big part of what CIRM does revolves around nurturing projects at the very early stages. By providing funding and guidance through our collaborative team of experts, CIRM de-risks its therapy development programs through pre-clinical and clinical stages, thereby readying them for industry partnerships to support them through the last mile. CIRM funding to California academic institutions has enabled the launch of more than 40 spinout companies, one of which we will highlight below.

On April 7th, 2020, Forty Seven, Inc. was acquired by Gilead Sciences for $4.9 billion. CIRM funded the preclinical and early clinical development of an anti-CD47 antibody candidate for cancer at Stanford and subsequently funded two Forty Seven clinical trials. Now, Gilead will leverage all of its resources to accelerate the development of this promising cancer immunotherapy.

Dr. Mark Chao, Co-Founder, Forty Seven, Inc. had this to say about CIRM.

“CIRM’s support has been instrumental to our early successes and our ability to rapidly progress Forty Seven’s CD47 antibody targeting approach with magrolimab. CIRM was an early collaborator in our clinical programs and it’s support was instrumental in helping us reach a point where we could become a part of Gilead and move forward with our research.”

To proactively enable more partnering successes such as Forty Seven, CIRM has established the Industry Alliance Program (IAP) as a direct opportunity for the industry to partner with CIRM grantees in accelerating the most promising stem cell, gene and regenerative medicine therapy programs to commercialization. Through the IAP, CIRM is a dedicated and proactive partner to industry and CIRM grantees.

We recently launched a website for those interested in knowing more about these partnerships. It describes the IAP program in more detail can be accessed by clicking here.

If you are a potential industry partner wishing to learn more about CIRM’s IAP, please contact:

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.

CIRM’s Industry Alliance Program: Facilitating Partnerships to Advance Stem Cell Therapies

Some things are better together. Take for instance macaroni and cheese, eggs and bacon, cookies and ice cream. Each of these things are fine on their own, but together, they become something more powerful and delicious.

The right partnerships can bring out the best in things. At CIRM, we fully embrace this concept. That’s why we’re launching the Industry Alliance Program (IAP). It’s a new partnering opportunity to bring the most promising stem cell, gene therapy, and regenerative medicine programs to market where they can help people with unmet medical needs.

CIRM is the world’s largest stem cell research funding institution dedicated to helping patients by accelerating the development of quality stem cell treatments. We’re currently funding 244 active stem cell research programs including 39 ongoing clinical trials.

The CIRM IAP is designed to give pharma, biotech and VC firms direct access to CIRM’s growing stem cell portfolio. These partners work in the stem cell and regenerative medicine field and will be connected to CIRM-funded scientists working on projects relevant to their interests.

In a news release, CIRM’s President and CEO, Dr. Maria T. Millan, explained:

Maria T. Millan

“The goal of the IAP is to secure industry partnerships and funding for CIRM’s translational and clinical-stage projects. Our Agency provides researchers the initial funding to advance promising projects towards the clinic. Now, we’re going a step further by offering a program that facilitates connections between industry partners and our grantees. These companies can offer support or additional funding needed to give these promising projects the best chance for success and the best chance of helping patients.”

The first two companies to join the IAP are BlueRock Therapeutics and Vivo Capital. BlueRock is a Cambridge, Massachusetts-based company that is pioneering cell therapies for degenerative diseases while Vivo Capital is a global venture capital firm that invests in life sciences and healthcare companies.

CIRM will continue to selectively recruit new partners to the IAP with the goal of building a collaborative network to support the development and commercialization of CIRM-funded programs.

Neil Littman, CIRM’s Director of Business Development, concluded:

Neil Littman

“The IAP is essentially a built-in concierge service for the stem cell space. Our unique vantage-point both inside and outside of California – spanning discovery, translation, and clinical trials – allows us to effectively match CIRM-funded programs with the strategic objectives of our IAP partners.  We’re excited to work with partners such as BlueRock and Vivo who have a demonstrated commitment to advance stem cell-based therapies to the market.”

For more information about CIRM’s new IAP program, visit our website.