Main menu

Category: Press Release

Method targets the epigenome, makes no changes to the underlying DNA sequence
 First example of lasting repression after transient epi-editor delivery in a non-human primate 

DURHAM, N.C. and SEATTLE, WA -(BUSINESS WIRE)- May 22, 2023 – Last week, at the 26th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT), leading epigenetic editing company Tune Therapeutics showcased the power and potential of its TEMPO TM genetic tuning platform, by presenting data showing the stable repression of the PCSK9 gene and the effective reduction of LDL-cholesterol levels in non-human primates (NHPs). This data marks a significant waypoint on the path to epigenetic medicine, in that it represents the first demonstration of durable epigenetic gene regulation, in a large animal model, following transient delivery of an epi-editor.

A common therapeutic target for the prevention of cardiovascular disease, it is well established that repressing the PCSK9 gene reduces elevated LDL-cholesterol levels, in turn associated with the formation of artery-clogging plaques. The non-human primate data presented at the ASGCT conference showed that epigenome editing (or genetic tuning) can drive the stable repression of PCSK9 (ongoing past four months) following a single treatment, and without cutting or nicking the DNA, or altering its coding sequence in any way.

Tune’s TEMPO platform is based on decades of foundational research by company Co-Founders Charles Gersbach and Fyodor Urnov. The versatile, modular platform incorporates a DNA-binding Domain (DBD) that binds to DNA without cutting it, tethered to one or more effector proteins, which produce the required epigenetic effect. Depending on the effector selected, this can mean repressing genes that actively drive disease, or activating genes for which deficiency is the problem. Moreover, the TEMPO platform itself can be used to screen for unique gene regulation targets – providing an integrated, high-throughput process that accelerates the initial phases of drug discovery and development.

In the live data presentation, entitled “Transient Delivery of Epigenome Editors Stably Represses PCSK9 and Lowers LDL Cholesterol in Non-Human Primates”, Senior Scientist Jennifer Kwon described how Tune developed a TEMPO epi-repressor targeting the PCSK9 gene, encoded it into RNA, and delivered it to cells and large animal subjects via lipid nanoparticle (LNP). Initial experiments in rapidly dividing liver cells showed gene repression levels of up to 98% with effects maintained for over 6 months, suggesting a stable, heritable, and highly durable mechanism.:

When a single dose of the same epi-repressor was delivered intravenously to three NHPs, researchers recorded:

  • ~75% drop in serum PCSK9 past 120 days of observation
  • ~56% reduction in LDL-cholesterol levels
  • Methylation patterns around the PCSK9 target site that were practically unchanged between day 7 and day 85 of the study

Taken together, these results show a potent and persistent genetic tuning effect, well tolerated by the animals, and validate epigenetic DNA methylation as the core mode of action. The study is ongoing, and the durability of gene repression will continue to be monitored.  

“In our journey to develop genetic tuning into a precise and robust therapeutic modality, these results are incredibly promising,” said Derek Jantz, Ph.D., Chief Scientific Officer at Tune Therapeutics. “Safe and durable gene silencing following the transient delivery of an epi-repressor in primates represents a major milestone for the field and a significant step toward enacting meaningful change for millions of patients suffering from common and chronic diseases.”

“This data is highly encouraging for the field,” added Matt Kane, CEO of Tune Therapeutics, “as it presents a broad proof-of-concept for liver-directed epi-editing and attests to the potential for genetic tuning to unlock common disease and regenerative medicine.”

At the same ASGCT meeting, Tune also showed new data on the application of epi-editing to cell therapies and immuno-oncology. In a detailed poster presentation, Tune scientists showed that HER2-targeting human CAR T-cells could be epigenetically modified ex vivo to enhance their ability to proliferate, persist, and control the growth of solid tumors in engrafted mice. This exciting data suggested that multiplexing (targeting and tuning two genes simultaneously) had a combined effect that surpassed that of each gene targeted in isolation – in effect remodeling the cell to create a more robust, tumor-killing phenotype.

“The progress we’ve seen over the last six months has been momentous,” says Kane. “It’s an exciting time for the field, and we’re thrilled to be leading it.”

Click below to view the full data sets

TuneTx Scientific Presentations


ASGCT Presentation Details

Title: Transient Delivery of Epigenome Editors Stably Represses PCSK9 and Lowers LDL Cholesterol in Non-Human Primates
Date & Time: Friday May 19th, 9:00-9:15AM PT
Location: Los Angeles Convention Center, Room 515AB
Link to Abstract: https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=15223 


Title: Precision-Targeted Epigenome Editing Enhances CAR T Functional Profiles and 
Anti-Tumor Activity
Date & Time: Thursday May 18th, 12:00-2:00PM PT
Location: Los Angeles Convention Center Exhibit Hall, Board # 1096
Link to Abstract: https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=13716

About Tune Therapeutics

With its versatile and powerful TEMPO epigenomic control platform, Tune Therapeutics is pioneering a new therapeutic modality that has the potential to fine-tune any gene network and unlock the full power and potential of regenerative medicine.

With deep experience and a passionate commitment to exploration and innovation, Tune is driving through an inflection point in the history of genetic medicine: from targeting a limited range of rare conditions, to addressing thousands of common and complex diseases for which no curative treatment is available.

Media Contact:

E: media@tunetx.com


The genetic tuning innovator adds pioneering genetic medicine expert and an accomplished biotechnology lawyer to its management team

DURHAM, N.C. & SEATTLE–(BUSINESS WIRE)–Today, leading epigenomic editing company Tune Therapeutics introduced two members to its leadership team: Chief Scientific Officer, Derek Jantz, Ph.D., and General Counsel, Zachary Hale, J.D.

Dr. Jantz comes to Tune with deep expertise in developing cell and gene therapeutic candidates through the use of innovative genomic technologies. Hale joins the company after over a decade of specialized legal work with biotechnology startups.

Tune’s genetic tuning platform, TEMPO, enables precise and durable changes to gene expression without risking permanent, off-target mutations across the genome. Dr. Jantz will spearhead the development of Tune’s transformative genetic tuning platform, which has the potential to target a broad range of common, complex, and multigenic diseases.

“Dr. Jantz’s experience in taking novel modalities from inception to preclinical and clinical-stage therapies makes him an ideal addition to our team. His knowledge in this area is unsurpassed, and we’re eager to incorporate his scientific expertise as we advance our TEMPO genetic tuning platform,” said Matt Kane, CEO of Tune Therapeutics.

Dr. Jantz co-founded Precision BioSciences in 2006 as co-inventor of a novel method for modifying the DNA-recognition properties of the I-Crel homing endonuclease, which in turn provided the foundation for the ARCUS genome editing platform. At Precision, he led the development of allogeneic CAR T and in vivo editing platforms, overseeing all research teams and serving on the board of directors. Dr. Jantz holds more than 50 patents relating to gene editing, gene therapy, and cancer immunotherapy, and is the author of more than a dozen gene-editing publications.

“I’m thrilled to be joining the team at Tune,” said Dr. Jantz. “I’m excited by the unique potential of the TEMPO platform to impact major world health challenges that I believe to be beyond the reach other technologies.”

As Tune’s new General Counsel, Zach Hale will oversee all of Tune’s legal affairs. He previously served as Senior Vice President and Deputy General Counsel at Juno Therapeutics, and before that was a corporate attorney at the international law firm Latham & Watkins LLP. He received his J.D. from Yale Law School and his B.A. summa cum laude from Harvard.

“Zach’s expertise specific to the biotechnology field makes him well-prepared to represent Tune as we rapidly expand,” said Akira Matsuno, Co-Founder, President, and Chief Financial Officer at Tune. “The entire leadership team anticipates Zach and Derek will accelerate our success.”

“I am honored to join the stellar group of scientists, engineers, and biopharmaceutical development professionals that have been assembled at Tune,” said Hale. “I look forward to supporting Tune in driving the development of cutting-edge epigenetic therapeutics, and making a serious difference in patients’ lives.”

“Derek and Zach are joining at a critical stage in our development,” Kane added. “Their leadership will be decisive in advancing a new and transformative class of precision genetic-tuning treatments.”

About Tune Therapeutics

With its versatile and powerful TEMPO epigenomic control platform, Tune Therapeutics is pioneering a new therapeutic modality that can fine-tune any gene network and unlock the full power and potential of regenerative medicine.

With deep experience and a passionate commitment to exploration and innovation, Tune is driving through an inflection point in the history of genetic medicine: from targeting a limited range of rare conditions, to addressing thousands of common and complex diseases for which no curative treatment is available.

Contacts

media@tunetx.com

Former Assembly Bio and Gilead exec brings decades of experience in developing novel therapeutics to Tune’s growing pipeline of genetic tuning therapies

DURHAM, N.C. & SEATTLE–(BUSINESS WIRE)–Tune Therapeutics, a biotechnology company pioneering the creation of genetic tuning (epigenomic editing) therapies, today announced the addition of John McHutchison AO, MD – former CEO at Assembly Biosciences, Inc., and CSO at Gilead Sciences, Inc. – to its board of directors. Dr. McHutchison joins as a noted industry leader with extensive experience in advancing novel treatments for the benefit of patients facing serious, intractable diseases.

“Dr. McHutchison’s experience will be pivotal as we advance our novel genetic tuning candidate therapies,” said Matt Kane, CEO of Tune Therapeutics. “John’s background in a broad range of modalities and therapeutic areas – right across the R&D spectrum – is incredibly well aligned with our mission to unlock the power of the epigenome in the treatment of common, complex, and multigenic disease. I very much look forward to working closely with John as we advance this modality to the clinic.”

This move marks Dr. McHutchison’s first since retiring as President and CEO of Assembly Biosciences at the end of 2022. At Assembly, he led the company’s progress in the anti-viral space before transitioning to the board of directors and chairing the Science and Technology Committee. Prior to Assembly, he served as Chief Scientific Officer and Head of Research and Development at Gilead Sciences, where he led the development of a broad range of liver-directed therapies, including the curative HCV antiviral regimens and investigational therapies against nonalcoholic steatohepatitis (NASH). John was also instrumental in Gilead’s transformative acquisition of Kite Therapeutics, and its subsequent leadership position in the CAR T cell therapy field.

“Now that precision tuning of the epigenome has become a reality, we are witnessing a critical moment for the future of medicine,” said Dr. McHutchison. “With its unique TEMPO platform, Tune Therapeutics is making great strides across a range of applications and diseases, the potential of which is enormous. I anticipate great things to come, and I am pleased to be supporting the company and its crucial and exciting work.”

About Tune Therapeutics

With its versatile and powerful TEMPO epigenomic control platform, Tune Therapeutics is pioneering a new therapeutic modality that can fine-tune any gene network and unlock the full power and potential of regenerative medicine. With deep experience and a passionate commitment to exploration and innovation, Tune is driving through an inflection point in the history of genetic medicine: from targeting a limited range of rare conditions, to addressing thousands of common and complex diseases for which no curative treatment is available.

Contacts

media@tunetx.com

World-leading researchers and venture-builders found company to mine the new frontier of epigenomics and unlock complex disease

Novel approach tunes and calibrates gene expression without breaking or rewriting DNA

Unique TEMPO platform targets complex gene networks, reveals the underlying, epigenomic drivers of disease, and yields optimized therapeutic candidates that shift cell state and function

Durham, N.C. and Seattle, December 2, 2021 – – Tune Therapeutics, a biotechnology company pioneering the creation of epi-therapeutic medicines, launched today with its powerful and precise genetic tuning platform, TEMPO. This cutting-edge technology dials gene expression up or down to desired levels – with the potential to reverse pathways of cancer, genetic disease, and aging by changing cell fate and function at will.

“Genetic medicine is at a tipping point,” said Matt Kane, CEO of Tune Therapeutics. “We now understand that the driving force of human health and disease is not our genes, but the epigenomic elements that shape and control them. Until now, scientists and bioengineers lacked the combined understanding, clinical expertise, and technology needed to make epigenomic therapies a practical reality. Now, we have all three.”

TEMPO Platform

Tune’s proprietary TEMPO platform can rapidly target and adjust the epigenomic machinery of the cell, which shapes DNA and controls gene expression. By varying specific control modules in an iterative process, TEMPO can fine-tune expression toward healthy levels – even in diseases involving multiplex or polygenic interactions.

Unlike genome editing, the tuning process does not generate double- or single-strand breaks in DNA and makes no permanent changes to the DNA sequence. This de-risks the precise targeting of entire gene networks, allowing Tune to simultaneously turn silenced genes on and dial over-expressed genes down, in a practical, therapeutic context.

Tune has already shown that TEMPO can locate epigenomic elements involved in several intractable genetic conditions – revealing targets and networks that would be invisible or inaccessible to gene editing approaches. Moreover, Tune can optimize TEMPO to command expression of individual genes or networks with remarkable specificity and precision. This opens the door to an entirely new class of epi-therapeutics.

“The exciting challenge in front of us is taking these transformative advances in technology and extending their potential for our greater society,” said Charlie Gersbach, PhD, Acting Chief Scientific Officer, Tune Therapeutics. “From proof of concept in rare, single-gene disorders to common conditions that aren’t linked to a single gene mutation – but are treatable through epigenomic control and constitute the vast majority of human diseases.”

Veteran Genomic Medicine Leadership Team

Tune is launching with a veteran leadership team, endowed with deep expertise in gene and cell therapy, genome editing, and epigenetics.

  • Matt Kane, Chief Executive Officer
  • Akira Matsuno, Co-Founder, President and Chief Financial Officer
  • Charlie Gersbach, Ph.D., Co-Founder, Acting Chief Scientific Officer
  • Fyodor Urnov, Ph.D., Co-Founder, Scientific Advisory Board
  • Heidi Zhang, Ph.D., Executive Vice President, Head of Technical Operations
  • Blythe Sather, Ph.D., Vice President, Head of Research

In addition, Tune’s Board of Directors includes Mr. Kane, Dr. Gersbach, Ali Behbahani, M.D., (New Enterprise Associates), and co-founder Dan McHugh (Emerson Collective).

Drawing upon deep, local talent pools in Durham and Seattle, Tune has assembled two highly seasoned discovery and development teams, secured foundational intellectual property from Duke University, and raised $40 million from top-tier investors – including co-leads New Enterprise Associates and Emerson Collective, with Hatteras Venture Partners, Mission BioCapital, and others joining the round. This financing will enable Tune to rapidly advance its preclinical research, attract top-tier talent, and further develop its therapeutic platform.

“Tune is effectively pioneering a brand-new therapeutic modality,” said Dr. Behbahani. “With the unbound potential of this approach, and their collective successes in the field, Tune is primed to become a transformative presence in modern biomedicine.”

About Tune Therapeutics

Tune Therapeutics, Inc. is orchestrating the power of the epigenome to treat complex, pervasive diseases that have long eluded treatment. With its versatile and powerful TEMPO epigenomic control platform, Tune’s experienced team is pioneering a new therapeutic modality that can fine-tune any gene network. In breaking free from the limitations of traditional gene and cell therapies, Tune is developing solutions for even the most challenging and intractable diseases – and building the capacity to transform human health and medicine.

###

Media Contact:
media@tunetx.com