In November 2017, Harvard University scientist Douglas Melton made headlines when his startup, Semma Therapeutics, raised $114 million in a series B funding round to develop what he said would be a potential cure for Type 1 diabetes. His idea was to take undifferentiated pluripotent stem cells and turn them into insulin-producing pancreatic beta cells.
Problem was, only 30% of the cells that emerged from the transformation process Melton’s lab developed turned out to be functioning beta cells. Now, his team of researchers says they figured out how to improve their process so they can increase the proportion of beta cells to 80%. They published their findings in the journal Nature.
Improvements in single-cell gene sequencing made it possible for Melton’s lab to probe all of the cells they were making from stem cells as they tried to transform them into beta cells. They discovered wide variations in gene expression among the cells. Some expressed genes consistent with glucagon production, while others had gene-expression patterns consistent with the sought-after insulin-producing beta cells.
The researchers also found a protein that’s expressed only on beta cells. That discovery allowed them to develop a hook method that could “fish” beta cells out of the mixture of cells that emerged from their process, according to a statement from Semma.
Scientists at Semma developed a second method to further boost the population of beta cells. They hypothesized that hormone-producing cells would be more attracted to each other than they are to non-hormone producers. So they physically separated all the cells and let them cluster back together naturally. It worked: The clustering further enriched the number of beta cells in each sample of converted stem cells, they reported.
RELATED: Reprogramming pancreatic cells into insulin makers to treat diabetes
Semma was founded in 2014, raising $44 million in a series A funding. The company formed a partnership with Novartis, which contributed to Semma’s series B round along with medical devices giant Medtronic, MPM Capital, ARCH Venture Partners and several other venture capitalists. In May of last year, Novartis veteran Bastiano Sanna moved to Semma to take over as CEO.
As Semma moves through the proof-of-concept stage of its development, several other research groups are examining different methods for regenerating insulin-producing cells. In February, researchers at the University of Geneva reported promising results in mouse models of diabetes with human alpha and gamma endocrine cells that had been converted into insulin-producing cells.
A team at the University of Miami is working on converting specialized stem cells called progenitors into beta cells. And Stanford University scientists recently discovered that zinc can aid in regenerating insulin-producing beta cells.
The next step for Semma’s team is to determine whether a mixture consisting of 80% beta cells will be appropriate for treating people with diabetes. They are planning further studies to determine the optimal mix of cell types.
“Maybe you need more of the other cell types to help regulate the beta cells, so that they function correctly,” said lead author Adrian Veres, a graduate student in Melton’s lab, in an interview with the Harvard Gazette. “We’re going to find out how the cell types interact with each other.”
Pivotal Study to Evaluate Potential of Anti-CD3 Monoclonal Antibody to Intercept Type 1 Diabetes
“PRV-031 (teplizumab) has the potential to be the first ever disease modifying therapy in T1D, and the first drug class approved for T1D since the introduction of insulin,” said Dr. Kevan Herold, M.D., Professor of Immunobiology and Medicine at Yale University. “Data from prior clinical studies have indicated the potential of PRV-031 (teplizumab) to preserve functional beta cell mass, thereby conserving natural insulin production and reducing the need for insulin therapy. PRV-031 (teplizumab) may therefore offer a much-needed improvement over currently approved treatment options for T1D. I commend the patients, the Provention team, and my fellow clinicians for undertaking this study and look forward to further exploring its potential impact in newly-diagnosed T1D patients.”
The PROTECT study is designed to confirm the effect of PRV-031 (teplizumab) to slow the loss of insulin-producing beta cells and preserve beta cell function, as measured by C-peptide, in children and adolescents 8-17 years old who have been diagnosed with T1D in the previous six weeks and with pre-specified beta cell reserve at study entry.
“The initiation of the PROTECT study represents a significant milestone in our efforts to develop agents that intercept or prevent immune-mediated diseases,” stated Ashleigh Palmer, CEO of Provention Bio. “If successful, this pivotal Phase 3 trial could serve as the basis for a Biologics License Application (BLA) for PRV-031 (teplizumab), providing a therapeutic option that could transform the therapeutic landscape for T1D.”
PROTECT Phase 3 Trial
The global PROTECT (PROvention T1D trial Evaluating C-peptide with Teplizumab) Phase 3 clinical trial is a randomized, double‑blind, placebo-controlled, multicenter trial that is expected to enroll approximately 300 patients ages 8-17 with recent onset T1D at approximately 80 centers worldwide. The patients will be randomized 2:1 to either two 12-day cycles, six months apart, of intravenous PRV-031 (teplizumab) or placebo. The primary efficacy endpoint is C-peptide change. Secondary endpoints include insulin use, HbA1c, hypoglycemic episodes, and safety. Provention expects to complete enrollment in the trial by the end of 2020.
Additional information is available at clinicaltrials.gov.
About PRV-031 (teplizumab)
PRV-031, also known as teplizumab, is an anti-CD3 monoclonal antibody (mAb), which is being developed for the interception of type 1 diabetes (T1D). Provention Bio acquired PRV-031 from MacroGenics, Inc. in May 2018. The candidate has been the subject of multiple clinical studies involving more than 1,000 subjects with more than 800 patients receiving PRV-031 in those studies. PRV-031 may also hold potential in the prevention or delay in onset of T1D and is currently being evaluated in the “At Risk” Study, a clinical trial conducted by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at TrialNet sites in relatives of T1D patients at risk for developing the disease.
About Provention Bio, Inc.
Provention Bio, Inc. (Nasdaq: PRVB) is a clinical-stage biopharmaceutical company leveraging a transformational drug development strategy that is focused on the prevention or interception of immune-mediated disease. Provention’s mission is to in-license, transform and develop therapeutic candidates targeting the high morbidity, mortality and escalating costs of autoimmune and inflammatory diseases including: type 1 diabetes (T1D), Crohn’s disease, ulcerative colitis, celiac disease, lupus, and certain life-threatening viral diseases. Provention’s diversified portfolio includes advanced-stage product development candidates that have undergone clinical testing by other companies. For more information on Provention Bio, please visit www.proventionbio.com.
Forward Looking Statements
Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Provention’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to failure to obtain FDA approvals or clearances and noncompliance with FDA regulations; uncertainties of patent protection and litigation; limited research and development efforts and dependence upon third parties; substantial competition; our need for additional financing and the risks listed under “Risk factors” in our annual report on Form 10-K for the year ended December 31, 2018 and any subsequent filings with the Securities and Exchange Commission (SEC). As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. Provention does not undertake an obligation to update or revise any forward-looking statement. The information set forth herein speaks only as of the date hereof.
Investors:
Kimberly Minarovich or Sam Martin, Argot Partners
Kimberly@argotpartners.com or Sam@argotpartners.com
212-600-1902
Media:
David Rosen, Argot Partners
David.Rosen@argotpartners.com
212-600-1902
SOURCE Provention Bio, Inc.
