Graphite Bio Presents Overview of Phase 1/2 CEDAR Trial Evaluating Investigational Gene Editing Therapy GPH101 in Sickle Cell Disease at 63rd ASH Annual Meeting and Exposition

Rhea-AI Summary

Graphite Bio presented a trial-in-progress poster for its Phase 1/2 CEDAR trial assessing GPH101, a gene therapy targeting sickle cell disease. The therapy aims to correct the genetic mutation causing the disease. Initial proof-of-concept data is expected by the end of 2022. GPH101 has received orphan drug designation from the FDA. This open-label trial will evaluate safety in about 15 participants with severe sickle cell disease, seeking to demonstrate the potential for a curative approach by restoring normal hemoglobin production.

Positive

• GPH101 has received orphan drug designation from the FDA.
• Initial proof-of-concept data from the CEDAR trial is anticipated by end of 2022.
• First patient enrolled in the CEDAR trial, indicating progress in development.

Negative

• Potential delays in patient enrollment and trial conduct due to risks associated with clinical trials.

Trial-in-progress poster presentation provides overview of first-in-human Phase 1/2 clinical trial in participants with severe sickle cell disease designed to evaluate safety, efficacy and pharmacodynamics of GPH101

Initial proof-of-concept data from CEDAR trial anticipated by end of 2022

GPH101 granted orphan drug designation from the U.S. Food & Drug Administration

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Graphite Bio, Inc. (Nasdaq: GRPH), a clinical-stage, next-generation gene editing company focused on therapies that harness targeted gene integration to treat or cure serious diseases, today presented a trial-in-progress poster for the company’s Phase 1/2 CEDAR trial for GPH101, an investigational therapy designed to directly correct the genetic mutation responsible for sickle cell disease (SCD). The poster is being presented at the 63rd American Association of Hematology (ASH) Annual Meeting and Exposition taking place virtually and at the Georgia World Congress Center in Atlanta from December 11-14. GPH101 was recently granted orphan drug designation from the U.S. Food and Drug Administration (FDA).

“Sickle cell disease is a devastating illness for which a cure is desperately needed. By directly correcting the mutation that causes sickle cell disease, we believe that GPH101 has the potential to be a one-time cure that restores normal physiology and alleviates the life-threatening morbidities associated with the disease,” said Josh Lehrer, M.Phil., M.D., chief executive officer at Graphite Bio. “We are excited to share details about our CEDAR clinical trial for GPH101, in which we recently enrolled our first patient, and we look forward to continuing to advance GPH101’s development in anticipation of sharing initial proof-of-concept data by the end of next year.”

The trial-in-progress poster is being presented by Julie Kanter, M.D., associate professor of medicine and co-director of the Comprehensive Sickle Cell Center at the University of Alabama at Birmingham and an investigator in the CEDAR trial.

“While allogeneic transplant is the only available cure for sickle cell disease, the procedure has several limitations, mainly lack of available donors and risk of graft-versus-host disease. Other available therapies are considered palliative as they do not specifically reverse end-organ damage. This type of gene therapy – reducing sickle hemoglobin production at the same time as restoring adult hemoglobin expression through direct gene correction – would be an ideal curative option in sickle cell disease,” said Dr. Kanter. “As an investigator in the CEDAR trial, I look forward to assessing GPH101’s potential to be a curative option for patients.”

The CEDAR trial is an open-label, single-dose, multi-site clinical trial evaluating GPH101 in approximately 15 participants with severe SCD. GPH101 is an autologous hematopoietic stem cell therapy developed using Graphite Bio’s next-generation targeted gene integration platform, which uses high-fidelity Cas9 and a non-integrating DNA template to precisely find the genetic mutation in the beta-globin gene and directly correct the mutation through the cell’s natural homology directed repair (HDR) cellular pathway. GPH101 has demonstrated in preclinical studies the potential to permanently reduce sickle hemoglobin (HbS) production and restore adult hemoglobin (HbA) expression. The trial-in-progress poster provides an overview of the GPH101 treatment process, which includes local stem cell selection and cryopreservation before shipment to a central manufacturing facility.

The primary objective of the CEDAR trial is to evaluate the safety of GPH101. Secondary objectives include pharmacodynamic and efficacy read-outs such as levels of HbA, HbS and total hemoglobin and effect on clinical manifestations such as vaso-occlusive crisis and acute chest syndrome. Additionally, characterization of gene correction rates, changes in the function of organs like the brain, heart, kidney and liver, and assessment of red blood cell health and function will be explored.

The poster is now available on the ASH website and on the Graphite Bio website here. Details are as follows:

Poster Session: 801. Gene Therapies: Poster I
Poster #1864: CEDAR Trial in Progress: A First in Human, Phase 1/2 Study of the Correction of a Single Nucleotide Mutation in Autologous HSCs (GPH101) to Convert HbS to HbA for Treating Severe SCD
Presenting Author: Julie Kanter, M.D., University of Alabama at Birmingham
Date/Time: Saturday, December 11, 2021, 5:30-7:30 p.m. ET
Location: Hall B5 (Georgia World Congress Center)

About Sickle Cell Disease (SCD)

SCD is a serious, life-threatening inherited blood disorder that affects approximately 100,000 people in the United States and millions of people around the world, making it the most prevalent monogenic disease worldwide. SCD is caused by a single mutation in the beta-globin gene that leads red blood cells to become misshapen, resulting in anemia, blood flow blockages, intense pain, increased risk of stroke and organ damage, and reduced life expectancy of approximately 20-30 years. Despite advancements in treatment and care, progressive organ damage continues to cause early mortality and severe morbidity, highlighting the need for curative therapies.

About GPH101

GPH101 is an investigational next-generation gene-edited autologous hematopoietic stem cell (HSC) therapy designed to directly correct the genetic mutation that causes sickle cell disease (SCD). GPH101 is the first investigational therapy to use a highly differentiated gene correction approach that seeks to efficiently and precisely correct the mutation in the beta-globin gene to decrease sickle hemoglobin (HbS) production and restore normal adult hemoglobin (HbA) expression, thereby potentially curing SCD.

Graphite Bio is evaluating GPH101 in the CEDAR trial, an open-label, multi-center Phase 1/2 clinical trial designed to assess the safety, engraftment success, gene correction rates, total hemoglobin, as well as other clinical and exploratory endpoints and pharmacodynamics in patients with severe SCD.

About Graphite Bio

Graphite Bio is a clinical-stage, next-generation gene editing company harnessing high efficiency targeted gene integration to develop a new class of therapies to potentially cure a wide range of serious and life-threatening diseases. Graphite Bio is pioneering a precision gene editing approach that could enable a variety of applications to transform human health through its potential to achieve one of medicine’s most elusive goals: to precisely “find & replace” any gene in the genome. Graphite Bio’s platform allows it to precisely correct mutations, replace entire disease-causing genes with normal genes or insert new genes into predetermined, safe locations. The company was co-founded by academic pioneers in the fields of gene editing and gene therapy, including Maria Grazia Roncarolo, M.D., and Matthew Porteus, M.D., Ph.D.

Learn more about Graphite Bio by visiting www.graphitebio.com and following the company on LinkedIn.

Forward-Looking Statements

Statements we make in this press release may include statements which are not historical facts and are considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact, including statements regarding the clinical and therapeutic potential of our gene editing platform and our product candidates, and the timing for treating the first patient in the Phase 1/2 CEDAR trial of GPH101 and the availability of initial proof-of-concept data, may be deemed to be forward-looking statements. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act and are making this statement for purposes of complying with those safe harbor provisions.

Any forward-looking statements in this press release are based on Graphite Bio’s current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements, including the risk that we may encounter delays in patient enrollment and in the initiation, conduct and completion of our planned clinical trials. These risks concerning Graphite Bio’s programs and operations are described in additional detail in its periodic filings with the U.S. Securities and Exchange Commission, including but not limited to the Company’s most recently filed periodic report. Graphite Bio is providing the information in this press release as of this date and explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20211211005014/en/

Company Contact:

Stephanie Yao

VP, Communications and Investor Relations

443-739-1423

syao@graphitebio.com

Investor Relations:

Stephanie Ascher

Stern IR, Inc.

212-362-1200

ir@graphitebio.com

Media Contact:

Christy Curran

Sam Brown, Inc.

615-414-8668

media@graphitebio.com

Source: Graphite Bio, Inc.

FAQ

What is the purpose of the GPH101 trial?

The GPH101 trial aims to evaluate the safety and efficacy of a gene therapy designed to directly correct the mutation that causes sickle cell disease.

When is the initial proof-of-concept data for GPH101 expected?

Initial proof-of-concept data from the CEDAR trial is anticipated by the end of 2022.

What designation has GPH101 received from the FDA?

GPH101 has been granted orphan drug designation by the FDA.

How many participants will the CEDAR trial evaluate?

The CEDAR trial will evaluate approximately 15 participants with severe sickle cell disease.

What are the main objectives of the CEDAR trial?

The primary objectives include assessing the safety of GPH101, with secondary objectives focusing on pharmacodynamics and efficacy read-outs.