- Cristian Massacesi, M.D., Chief Medical Officer of AstraZeneca and Alexion and Oncology Chief Development Officer of AstraZeneca, to support Replay in advancing genomic medicine and cell therapy pipeline
- Dr. Massacesi brings over 20 years of research and medicines development experience to the Replay Board

__San Diego, California and London, UK, May 25, 2023__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced the appointment of Cristian Massacesi, M.D., as a member of its Board of Directors, with immediate effect.

Dr. Massacesi is a leading expert in medical oncology, with over 20 years of research and drug development experience in the pharmaceutical industry. Dr. Massacesi is the Chief Medical Officer of AstraZeneca and Alexion, where he oversees patient safety and quality assurance activities for the entire company portfolio – from investigational drugs to established products. He is also the Oncology Chief Development Officer at AstraZeneca, where he leads the global development and operations of its late-stage Oncology portfolio of innovative medicines and immunotherapies, comprising more than 160 studies spanning multiple indications. His role and responsibilities at AstraZeneca continue unchanged.

Prior to AstraZeneca, Dr. Massacesi held several other senior leadership roles. He was Vice President, and Medicine Team Leader Immuno-Oncology at Pfizer, where he led multiple development programs in lung cancer, head and neck cancer, and hematological malignancies, and supported the oncology business development and pipeline strategy.

Dr. Massacesi was also Vice President, and Senior Global Clinical Program Head for the Immunotherapy Centre of Excellence at Novartis, and the Oncology Global Development and Global Medical Affairs Paris Site Head. Prior to that, as Global Clinical Program Head, he led the company’s PI3K-inhibitors portfolio through clinical development, including registrational studies and submissions.

Dr. Massacesi began his Academic career at Marche Polytechnic University in Italy, where he worked in the Department of Medical Oncology and Radiotherapy. He holds postgraduate degrees from the School of Oncology and School of Forensic Medicine at Marche Polytechnic University and received his medical oncology training at the Royal Marsden Hospital in London, UK, the Kaplan Comprehensive Cancer Center, NY, USA, and the European Institute of Oncology, Italy.

Dr. Massacesi has authored over 50 peer-reviewed papers and 100 conference abstracts on a wide range of cancer topics and lectured on subjects that include immunotherapy clinical trials, breast cancer, and the clinical development of PI3K-inhibitors. Dr. Massacesi has authored multiple patents on cancer treatment combinations and regimens.

__Adrian Woolfson, Executive Chairman, President, and Co-founder of Replay__, commented: “Cristian has an exceptional reputation within the life sciences community and his extensive experience and expertise in leading oncology clinical development programs is a significant addition to Replay’s board. His breadth of industry knowledge, especially in the field of immuno-oncology, will be invaluable to Replay’s continued growth, as we build out our first-in-class portfolio of TCR-NK cell therapies and HSV-based gene therapies to address some of the most significant challenges in cell therapy and genomic medicine. On behalf of the Board of Directors, I am delighted to welcome Cristian to the company and look forward to working with him as we continue to build an enduring enterprise with the potential to shape the future of the industry.”

__Lachlan MacKinnon, CEO and Co-Founder of Replay__, added, “Replay’s genomic medicine toolkit encompasses a broad portfolio of disruptive platform technologies to write and deliver big DNA that we are advancing within our distinct hub-and-spoke business model. Our Board brings together unrivalled expertise across a wide range of specialties that support this, and Cristian’s unique knowledge and skill set, especially within the immuno-oncology space, will be invaluable as we continue to drive the strategy forward.”

__Kugan Sathiyanandarajah, Managing Director at KKR and Board Member at Replay__, stated, “We are thrilled to have Cristian joining the Board. His extensive experience in oncology drug development within the pharmaceutical industry will be of immense value as Replay transitions into a clinical-stage company with the potential to significantly impact the healthcare sector.”

Commenting on his appointment, __Cristian Massacesi__ said, “Replay has the potential to transform the future of cell therapy and genomic medicine in general through its unique portfolio of technology platforms and innovative approach to product development. I am excited to be joining as a board member and to be supporting such a strong and dynamic team. It’s a pivotal moment in the company’s development as it progresses its first-in-class, engineered TCR-NK cell therapies and HSV-based gene therapies into the clinic, and I’m pleased to be able to bring my knowledge and experience to help Replay’s mission.”

__Ends__

__About Replay__

Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The company has assembled a toolkit of disruptive platform technologies – including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing platform – to address the challenges currently limiting clinical progress and preventing genomic medicine from realizing its full potential.

The company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in a portfolio of product companies that leverage its technology platforms. For example, the Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company using technology developed by Professor Katy Rezvani at the MD Anderson Cancer Center in Houston, Texas. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. Replay is led by a distinguished team of academics, entrepreneurs, and industry experts.

The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners.

Replay is headquartered in San Diego, California. For further information please visit www.replay.bio and follow us on LinkedIn and Twitter.

__Contacts:__

__Replay__

Dr Adrian Woolfson/Lachlan MacKinnon

info@replay.bio

__Consilium Strategic Communications – Media relations__

Amber Fennell/David Daley /Melissa Gardiner

replay@consilium-comms.com


Cristian Massacesi, M.D., Appointed to Replay Board of Directors


- Arun Balakumaran M.D., Ph.D, appointed Chief Medical Officer of Replay to support the Company’s genomic medicine and engineered NK cell therapy pipeline
- Former Chief Medical Officer of allogeneic CAR-T cell company Allogene Therapeutics and seasoned industry immuno-oncology, and cell and gene therapy expert 
- Dr. Balakumaran also appointed CMO of Syena, Replay’s engineered NK cell therapy product company pioneering first-in-class engineered T-cell Receptor Natural Killer cell (TCR-NK) therapy

__San Diego, California and London, UK, May 18, 2023__ – Replay, a genome writing company reprogramming biology by writing and delivering big DNA, today announced the appointment of Arun Balakumaran, M.D., Ph.D., as Chief Medical Officer (CMO), effective 22 May.

An expert in immuno-oncology and cell and gene therapy, Dr. Balakumaran brings more than 15 years of clinical development experience at leading biotechnology and pharmaceutical companies, including Merck and Amgen, to the Company. At Replay, Dr. Balakumaran will support the clinical development of Replay’s differentiated portfolio of next-generation genomic medicines and technology platforms, including its first-in-class engineered TCR-NK cell therapy programs that are anticipated to enter the clinic later this year. 

Dr. Balakumaran joins Replay from Allogene Therapeutics (NASDAQ: ALLO), where he served as CMO and Senior Vice president, overseeing the Company’s clinical development strategy across multiple allogeneic cell therapy programs. Prior to that, he held roles of increasing seniority at Merck (NASDAQ: MRK), where he was the Product Development Lead for Hematological Malignancies and led the activities resulting in breakthrough designations and the eventual approval of Pembrolizumab® in lymphoma. Prior to that he was Clinical Research Medical Director at Amgen (NASDAQ: AMGN), and Medical Lead in Oncology. 

Dr. Balakumaran began his career at the National Institutes of Health (NIH), where he was Medical Lead for the Bone Marrow Stromal Cells (MSC) Transplant Center. He is a board-certified hematologist and medical oncologist and holds a Master’s degree in healthcare management from Harvard University. Dr. Balakumaran also serves on the Board of Onco Filtration Inc. and the Scientific Advisory Board of SDS Optic.

Dr. Balakumaran will, additionally, join Replay’s engineered TCR-NK cell therapy product company Syena as CMO, where he will support the clinical development of its first-in-class and first-in-human engineered TCR-NK cell therapy clinical programs in both hematological malignancies and solid tumors. Syena was co-founded by Professor Katy Rezvani, M.D., Ph.D., and is developing a scalable, off-the-shelf, cord blood-derived engineered TCR-NK platform, which was licensed exclusively from The University of Texas MD Anderson Cancer Center, in February 2023.

__Adrian Woolfson, Executive Chairman, President, and Co-Founder of Replay__, commented: “Arun’s extensive expertise across cell and gene therapy, and immuno-oncology, will be invaluable for Replay and its product companies, including our first-in-class engineered TCR-NK cell therapy company, Syena. He will be joining a rapidly expanding team of world-class industry experts, academics, and entrepreneurs at Replay, where we are focused on delivering new therapeutic options for some of the key global medical challenges addressable using genomic medicine and engineered cell therapies. We are delighted to welcome him into our team.”

__Lachlan MacKinnon, CEO and Co-Founder of Replay__, added, “We have watched Arun’s progress at Allogene Therapeutics where he has been instrumental in advancing their allogeneic cell therapy programs into the clinic. His knowledge and experience will be of critical importance to the Company as we progress our genomic medicine pipeline, including the first-in-class TCR-NKs that we are developing within our engineered TCR-NK cell therapy product company, Syena.”

“Replay has the potential to transform the future of genomic medicine through its suite of genomic medicine platform technologies, engineered cell therapies, and innovative approach to corporate structure and product development,” said __Dr. Arun Balakumaran, Chief Medical Officer of Replay__. “The engineered TCR-NK platform that is being developed in Syena in particular, provides the promise of a highly scalable and off-the-shelf cell therapy with the potential to evade the primary mechanism of acquired resistance in existing cell therapies, through their innate anti-tumor activity. I look forward to working with the Replay executive team, Katy Rezvani at MD Anderson, and the Syena team to progress engineered TCR-NKs and the Company’s other programs and technologies including HSV-based gene therapy, into the clinic for the benefit of patients with high unmet medical needs.”

__Ends__

__About Replay__

Replay is a genome writing company, which aims to define the future of genomic medicine through reprogramming biology by writing and delivering big DNA. The Company has assembled a toolkit of disruptive platform technologies – including a high payload capacity HSV platform, a hypoimmunogenic cell therapy platform, and a genome writing platform – to address the scientific challenges currently limiting clinical progress and preventing genomic medicine from realizing its full potential. The Company’s hub-and-spoke business model separates technology development within Replay from therapeutic development in product companies that leverage its technology platforms. For example, the Company recently incorporated a first-in-class engineered TCR-NK cell therapy product company developed by Professor Katy Rezvani at the MD Anderson Cancer Center. Replay’s synHSV™ technology, a high payload capacity HSV vector capable of delivering up to 30 times the payload of AAV, is utilized by Replay’s four gene therapy product companies, bringing big DNA treatments to diseases affecting the skin, eye, brain, and muscle. Replay is led by a world-class team of academics, entrepreneurs, and industry experts. 

The Company raised $55 million in seed financing in July 2022 and is supported by an international syndicate of investors including: KKR, OMX Ventures, ARTIS Ventures, and Lansdowne Partners. 
Replay is headquartered in San Diego, California, and London, UK. For further information please visit www.replay.bio and follow us on LinkedIn and Twitter.  

__Contacts:__

__Replay__

Dr Adrian Woolfson / Lachlan MacKinnon
info@replay.bio

__Consilium Strategic Communications – Media relations__

Amber Fennell / David Daley / Melissa Gardiner 
replay@consilium-comms.com


Replay Appoints Arun Balakumaran M.D., Ph.D as Chief Medical Officer

endpts.com

31 Katy Rezvani light green

Cell and gene therapy biotech creator Replay plucks Allogene CMO Arun Balakumaran to lead clinical trials

While significant progress has been made in the field of genomic medicine, substantive challenges remain in achieving its tremendous potential. 

83% of genes are too big to be accommodated by the adeno-associated virus (AAV) vector, which is the current standard platform for gene delivery. As a result, our ability to treat the majority of diseases of global significance, which are complex, polygenic diseases caused by multiple genes, is limited. 

Replay aims to address this issue using its synHSV™ high payload capacity technology platform, which can deliver up to 30x the payload of AAV and that enables genes to be delivered in their natural form.

Matt Mulvey, Chief Technology Officer at Replay, explains more:

“DNA is the digital instruction code for life. It is what allows life on Earth to exist and propagate. Since it is a codescript, it can be modified, either gradually over time through evolution by natural selection, or as a result of intentional engineering, to adapt life to new environments or to generate new functions.

The field of synthetic biology attempts to transform the DNA code into a read/write medium capable of achieving specific purposes in biology. When the mechanism by which the DNA code specifies protein sequences was deciphered and scientists could assemble small DNA pieces, it enabled proteins to be manufactured on an industrial scale. The most common form of this process is the industrial production of therapeutic enzymes and antibodies that have been approved for the treatment of a broad range of diseases. 

![HSV: 150kb vs. AVV: 4.8kb](//images.ctfassets.net/g16a9pxiy3in/2mTox417u3I1A82ch0bBVn/1be60283f3d62018f6333aa6f2cca666/hsv-avv-2.png)

New emerging technologies will soon be available that will allow scientists to rapidly and efficiently synthesize and assemble large pieces of DNA, known as ‘Big DNA’. 

This will allow the science of synthetic biology to go beyond the limitations of current approaches and to create and administer genomically rewritten or ‘reprogramed’ cells to treat human diseases. Ultimately, as the ability to write Big DNA improves, it will become possible to redesign and build entire genomes to generate synthetic organisms of industrial and medical significance. 

A key challenge in the development of Big DNA therapeutics is how to efficiently deliver them to cells and ensure that they are functional and behave in a physiological manner. At Replay we have, amongst other things, developed synHSV™, a high payload capacity HSV vector capable of delivering large genes, genomic genes, multiple genes and multiple transcriptional regulators. This capability has the potential to extend the reach of genomic medicines and has the possibility to transform the therapeutic landscape for patients.”


Replay Bio Construct Illustration

Ask the Experts with Matthew Mulvey: What is “Big DNA”?

Home Page Hero

Home Page Applications 1-5kb

Writing Genes

- Rapid and cost-effective gene synthesis 
- Synthetic gene library generation 
- Rewrite and optimise gene sequences


Home Page Applications 1-5 Content

Home Page Applications 5-150kb

- Write and deliver big genes, genomic genes, and multiple genes 
- Complex regulatory elements and synbio circuitry
- Multiplex transcription factors in conjunction with control elements
- Polygenic medicine

Home Page Applications In Vivo

- Deliver big DNA to autologous, allogeneic, and iPSC-derived cell therapies
- Write and install large constructs to replace multiplex editing 
- Enable extensively genomically rewritten iPSC-derived therapies
- Regenerative medicine, CARs, TCRs
- Multiple cell types 

Home Page Applications Ex Vivo

Home Page Applications 150kb-10Mb

- Viral genomes (EBV : 170kb)
- Bacterial genomes (E.coli : 4.6mb)
- Mini Y chromosome (Human Y : 57mb) 

Home Page Applications 150kb-10MB

Home Page Applications 10mb-10gb+

Replay Leaf Cells

- Synthetic human chromosomes for iPSC-derived cell therapy
- Synthetic plant, fungal, and mammalian genomes

Home Applications Complex Genomes Content

Authoring the next generation of genomic products, leveraging synthetic gene libraries, high payload delivery, and hypoimmunogenic technologies.

Reprogramming biology by writing and delivering big DNA

Latest news

Cristian Massacesi, M.D., Appointed to Replay Board of Directors

Replay Appoints Arun Balakumaran M.D., Ph.D as Chief Medical Officer

Cell and gene therapy biotech creator Replay plucks Allogene CMO Arun Balakumaran to lead clinical trials

Ask the Experts with Matthew Mulvey: What is “Big DNA”?