Provention Bio Announces Publication of Extended Follow-up Data from the Pivotal "At-Risk" TN-10 Study of Teplizumab in Science Translational Medicine

RED BANK, N.J., March 3, 2021 /PRNewswire/ -- Provention Bio, Inc. (Nasdaq: PRVB), a biopharmaceutical company dedicated to intercepting and preventing immune-mediated disease, today announced that extended follow-up data from the pivotal "At-Risk" TN-10 Study were published in Science Translational Medicine. Results show that a single 14-day infusion course of teplizumab (PRV-031) delayed the onset of clinical disease and insulin dependence in at-risk type 1 diabetes (T1D) patients by approximately three years (median of 32.5 months), adding one year to previously reported results. The TN-10 Study was conducted through the Type 1 Diabetes TrialNet, an international research collaboration aimed at discovering ways to delay or prevent type 1 diabetes.

Teplizumab, Provention's lead drug candidate, is an anti-CD3 monoclonal antibody currently under review by the U.S. Food and Drug Administration (FDA) for the delay or prevention of clinical T1D in at-risk individuals, defined as having two or more T1D-related autoantibodies and dysglycemia (Stage 2 T1D). The lifetime risk of insulin-dependent clinical disease (Stage 3 T1D) approaches 100% in these pre-symptomatic Stage 2 patients.

"Teplizumab is the first disease-modifying investigational drug with data showing an ongoing delay to insulin-dependent T1D, now by approximately three years after a single course," said Dr. Kevan Herold, M.D., Professor of Immunology and Medicine at Yale University, lead author of the study. "These data build on existing clinical evidence demonstrating the potential for teplizumab to change the course of the disease and advance the treatment paradigm. We are continuing to observe patients in the TN-10 Study to determine whether the observed delay will extend even further over time."

The median time to clinical T1D was approximately 5 years in teplizumab-treated patients compared to slightly over 2 years in the placebo group. At this median follow-up of 2.5 years, twice as many teplizumab-treated patients remained free of clinical T1D compared to patients in the placebo group, 50% vs 22% respectively, (HR=0.457 p=0.01).

"It is very encouraging to see that a single course of teplizumab delayed insulin dependence in this high risk population for approximately three years versus placebo," said Frank Martin, Ph.D., JDRF Director of Research. "These exciting results have been made possible by the unwavering efforts of TrialNet and Provention Bio. Teplizumab, if approved by the FDA, could positively change the course of disease development for people at risk of developing T1D and their standard of care." 

The following includes key additional data and analysis from the publication:

• Teplizumab treatment improved beta cell function, with an average on-study C-peptide AUC of 1.96 vs 1.68 pmol/ml, p=0.006.
• Initiation of teplizumab treatment reversed the decline in C-peptide levels while controls continued to decline (p=0.0015). The changes in C-peptide with teplizumab treatment were associated with increases in partially exhausted memory KLRG1+ TIGIT+ CD8+ T cells (r=0.44; p=0.014) that showed reduced secretion of IFN-gamma and TNF-alpha.
• Total and early insulin secretory capacity was improved with teplizumab treatment suggesting improvement in beta cell glucose sensitivity reflecting normal beta cell function.
• Teplizumab was well tolerated, and the safety data is consistent with previous analyses.

"These data embolden our enthusiasm surrounding the potential impact teplizumab may have on the lives of T1D patients, families and caregivers," said Ashleigh Palmer, CEO and Co-Founder, Provention Bio. "Outcomes such as these validate Provention's mission to intercept and prevent debilitating and life-threatening diseases.  We continue working closely with the FDA in their review of our BLA submission for teplizumab. The PDUFA goal date is July 2, 2021."

About the Pivotal "At-Risk" TN-10 Study:
The "At-Risk" TN-10 Study, a pivotal Phase 2 clinical trial, evaluated teplizumab for the delay of insulin-dependent type 1 diabetes (Stage 3 of clinical T1D) in presymptomatic, Stage 2 or at-risk patients, defined by the presence of two or more T1D-related autoantibodies and dysglycemia. Seventy-six patients were enrolled ages 8 to 49, with 72% under the age of 18, and randomized to receive a single course of either teplizumab or placebo. Patients were followed in a blinded fashion until 40 of them developed clinical-stage T1D, and then indefinitely after the analysis of the randomized period data.

The study was conducted by TrialNet, a network of the world's leading T1D researchers, and funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and JDRF. The primary results were published in the New England Journal of Medicine and simultaneously presented at the 2019 American Diabetes Association's 79^th Scientific Sessions.

About Type 1 Diabetes (T1D):
Over 1.6 million Americans have type 1 diabetes (T1D), an autoimmune disease caused by the destruction of beta cells. T1D symptoms can take months or years to develop. The psychological impact of T1D is hard to quantity, but a diagnosis is life-altering, and regular monitoring and maintenance can be extremely stressful. T1D typically takes more than a decade off a person's life and life expectancy is reduced by 16 years on average for people diagnosed with T1D before the age of 10. Insulin is the current T1D treatment. It is necessary to keep patients alive, but it is a constant effort for patients. No disease-modifying treatments for T1D are currently available.

About Teplizumab (PRV-031):
Teplizumab is an investigational anti-CD3 monoclonal antibody (mAb) with a filed Biologics License Application (BLA) under Priority Review by the U.S. Food and Drug Administration (FDA) for the delay or prevention of clinical type 1 diabetes (T1D) in at-risk individuals. More than 800 patients have received teplizumab in multiple clinical studies involving more than 1,000 subjects. In previous studies of newly diagnosed patients, teplizumab consistently demonstrated the ability to preserve beta-cell function, a measure of endogenous insulin production. It correspondingly reduced the need for exogenous insulin use. Teplizumab has been granted Breakthrough Therapy Designation by the FDA and PRIME designation by the European Medicines Administration. Provention is currently also evaluating teplizumab in patients with newly diagnosed insulin-dependent T1D (the Phase 3 PROTECT study).

About JDRF:
JDRF's mission is to accelerate life-changing breakthroughs to cure, prevent, and treat T1D and its complications. To accomplish this, JDRF has invested more than $2.5 billion in research funding since our inception. We are an organization built on a grassroots model of people connecting in their local communities, collaborating regionally for efficiency and broader fundraising impact and uniting on a national stage to pool resources, passion and energy. We collaborate with academic institutions, policymakers and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with T1D. Our staff and volunteers throughout the United States and our five international affiliates are dedicated to advocacy, community engagement and our vision of a world without T1D. For more information, please visit jdrf.org or follow us on Twitter: @JDRF.

About Provention Bio, Inc.:
Provention Bio, Inc. (Nasdaq: PRVB) is a biopharmaceutical company focused on advancing the development of investigational therapies that may intercept and prevent debilitating and life-threatening immune-mediated diseases. The Biologics License Application (BLA) for teplizumab, its lead investigational drug candidate, for the delay or prevention of clinical type 1 diabetes in at-risk individuals has been filed by the U.S. Food and Drug Administration (FDA). The Company's pipeline includes additional clinical-stage product candidates that have demonstrated in pre-clinical or clinical studies proof-of-mechanism and/or proof-of-concept in other autoimmune diseases, including celiac disease and lupus. Visit www.ProventionBio.com for more information and follow us on Twitter: @ProventionBio.

Internet Posting of Information:
Provention Bio, Inc. uses its website, www.proventionbio.com, as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation F.D. Such disclosures will be included on the Company's website in the "News" section. Accordingly, investors should monitor this portion of the Company's website, in addition to following its press releases, SEC filings and public conference calls and webcasts.

Forward Looking Statements:
Certain statements in this press release are forward-looking, including but not limited to, statements relating to regulatory review of the BLA submission for teplizumab and the potential approval and commercial launch of teplizumab, including timelines relating to the same and the potential therapeutic effects and safety of teplizumab and the Company's product candidates. 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 the Company'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 delays in, or failure to obtain FDA approvals for teplizumab or other Company product candidates and the potential for noncompliance with FDA regulations; the potential impacts of COVID-19 on our business and financial results; changes in law, regulations, or interpretations and enforcement of regulatory guidance;  uncertainties of patent protection and litigation; the Company's dependence upon third parties; substantial competition; the Company's need for additional financing and the risks listed under "Risk Factors" in the Company's annual report on Form 10-K for the year ended December 31, 2020 and any subsequent filings with the Securities and Exchange Commission. 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, whether as a result of new information, future developments or otherwise, except as may be required by applicable law. The information set forth herein speaks only as of the date hereof.

Investor Contacts:

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484-639-7235

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Media Contact:
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Disclaimer: The content in this release is the sole responsibility of the authors and does not necessarily represent the official views or imply endorsement of the National Institutes of Health.

SOURCE Provention Bio, Inc.

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