Excision BioTherapeutics, Inc.

CAMBRIDGE, United Kingdom and NEW YORK, Feb. 07, 2024 (GLOBE NEWSWIRE) -- Artios Pharma Limited (“Artios”), clinical-stage biotech company led by pioneers of DNA damage response (“DDR”) drug development, announces the appointment of Christine Silverstein as Chief Financial Officer (CFO). Christine joins Artios with more than 15 years of diversified finance, corporate strategy, and business development experience in the biopharmaceutical industry. Niall Martin, Chief Executive Officer of Artios, said: “Christine is a seasoned CFO with robust capital markets expertise and a deep understanding of the industry landscape. We are pleased to welcome her to the Artios executive team where she will play a key leadership role in the U.S. and further strengthen our global presence. Importantly, her track record of raising capital, preparing companies for IPO, and experience with partnerships and M&A will position us for success as we continue to advance our leading DDR pipeline.” Before joining Artios, Christine most recently held executive leadership roles at Excision Biotherapeutics, Inc. and Emendo Biotherapeutics, where she successfully led financial strategy and corporate partnering, improved operational efficiency, and facilitated substantial growth. She will join the Company’s U.S. subsidiary in the New York office. Christine Silverstein, Chief Financial Officer of Artios, added: “As recognized innovators in DDR drug discovery, Artios’ advanced pipeline targeting the DNA damage response offers cutting-edge approaches for difficult-to-treat cancers. I am excited to join Artios at this pivotal time, with clinical data expected for lead programs including ATR inhibitor ART0380 and novel Pol theta inhibitor ART6043 over the next 12 months. I look forward to partnering with the Artios team as we approach this next stage of growth and work to advance potentially life-extending therapies for the treatment of a broad range of solid tumors.” Christine Silverstein has over 15 years of financial leadership experience spanning strategic and operational roles across both private and public biopharmaceutical companies. Prior to joining Artios, she most recently served as CFO of Excision Biotherapeutics, Inc., where she established numerous corporate functions and led financial planning, strategy, and initial public offering (IPO) readiness activities. Formerly as CFO of Emendo Biotherapeutics (acquired in December 2020 by AnGes, Inc.), Silverstein established the Company’s U.S. operations and capital market footprint for IPO preparedness as well as completed the M&A transaction. During her time at Abeona Therapeutics, Silverstein operated in multiple senior executive roles including CFO and Principal Financial Officer. Earlier in her career, she drove internal capital markets strategy at Relmada Therapeutics, Inc., and held senior executive roles within biotechnology venture fund SCO Capital Partners. Silverstein began her career in the financial services industry where she was instrumental in advising clients on transaction considerations and formulating effective U.S. public listing and financing strategies. Silverstein currently serves on the board of directors at Marinus Pharmaceuticals and Abeona Therapeutics Inc. Silverstein holds a B.S. from the Peter Tobin College of Business at St. John’s University and has earned various accreditations from the Financial Industry Regulatory Authority (FINRA) and Harvard University. About Artios Artios is on a mission to kill cancer by exploiting DNA damage response (DDR) and repair pathways that are leveraged by cancer cells to promote their survival. Our specialized DcoDeR platform integrates Artios’ leadership capabilities, expertise and experience in DNA damage biology and drug discovery to systematically discover and develop medicines targeting the totality of the DDR. We have built an extensive DDR focused pipeline designed to address areas of high unmet needs across solid tumour indications including our ATR inhibitor, ART0380, and our Polθ inhibitors, ART4215 and ART6043, as monotherapies and with combination treatments. Together with our strategic partnerships with Merck KGaA and Novartis, and research collaborations with premiere institutions like Cancer Research UK, The Institute of Cancer Research, The Netherlands Cancer Institute, and the Crick Institute we are pioneering validated approaches to DDR drug discovery. Visit our website at for more information about the company and our pipeline. For more information about Artios Pharma Ltd., please contact: Investor Relations Contact: LifeSci Advisors Alexandra Folias E: afolias@lifesciadvisors.com

Pictured: Illustration of gloved hands using tools to manipulate a DNA double helix/iStock, MicrovOne In the early 1990s, Mike McCune and his colleagues thought they’d found a path to a one-time HIV treatment for babies: genetically modifying hematopoietic stem cells to suppress the virus and then transplanting them into the bone marrow. But the treatment never made it to clinical trials. “It was not considered to be a good business plan,” he explained, because companies would make more money by selling these patients antiretroviral therapies for a lifetime than to deliver a one-time treatment. Vertex Pharmaceuticals and CRISPR Therapeutics’ Casgevy, which involves a process much like McCune’s HIV treatment—ex vivo gene editing of blood stem cells for the treatment of sickle cell disease (SCD) followed by transplantation back into the patient—did make it to market, having been recently approved by the FDA as the first CRISPR-based therapy. But Casgevy is pricy: it costs a whopping $2.2 million dollars. Its competitor Lyfgenia, another ex vivo gene therapy for SCD approved at the same time, carries a sticker price of $3.1 million. The high cost may limit access even for patients in the U.S., and will likely be a far more formidable barrier in sub-Saharan Africa, where 79% of babies with SCD are born. Now McCune and others are looking to bring gene therapy to the masses by developing treatments that involve treating cells in vivo, which could be far less costly than the ex vivo variety. Requiring only a single injection, the in vivo approach would use vectors to deliver DNA-changing machinery into cells. In the case of SCD, the target would be blood-making stem cells and the tweaks would induce them to make healthy hemoglobin, McCune explained; for HIV, viral DNA could be snipped inside infected cells to prevent viral replication and spread, as well as reinfection. While an existing in vivo gene therapies for rare genetic diseases also have eye-popping sticker prices, McCune argued that over time, costs will fall. McCune, now head of the Gates Foundation’s HIV Frontiers program, is helping to forge agreements between the philanthropy and multiple private companies with the aim of making gene therapy an accessible reality as a treatment for both HIV and SCD. And at least one biotech, Excision BioTherapeutics, is pursuing a similar approach to HIV treatment independently of Gates. The Economics of HIV Therapies As McCune sees it, there will be both a market and payers for a one-shot HIV treatment, both in the U.S. and in sub-Saharan Africa. He points out that the healthcare system is currently paying tens of thousands of dollars annually for each HIV patient in the U.S., money that could be redirected to paying for a cure. And in sub-Saharan Africa, he added, the U.S. is spending about $7 billion each year on antiretroviral treatment for people with HIV under a program called PEPFAR—funding that could likely cover the cost of a one-shot treatment instead. There’s no comparable payer for an SCD treatment, he said. “We have to work on that. And I think that’s going to become really important because the inequities of healthcare, so poignantly highlighted during COVID, are going to become even more glaringly obvious” now that there are multimillion-dollar treatments that are likely to remain inaccessible to many people with SCD. A Step Toward Broader Applications for In Vivo Treatments Gates has partnered with companies including Guide Therapeutics, bluebird bio, GreenLight Biosciences, Intellia Therapeutics, CRISPR Therapeutics, Immunocore, BioNTech, Vir, Ensoma, Emmune, Addition and Novartis, as well as nonprofits and academic labs, to work on aspects of in vivo gene therapy. The foundation has also partnered with the National Institutes of Health, which committed to kicking in $100 million toward the effort. Agreements with partners, McCune said, include a non-exclusive right for the Gates Foundation to make sure that the technologies are available to people living with HIV and SCD in low- and middle-income countries. “Why would they give us those rights?” he asked. Part of the answer is that “the applications of this platform are diverse, outside of the realm of HIV and sickle [cell disease] and into the realm of the more remunerative diseases that companies seem to focus on in the context of gene therapy,” including cancer. “They would see this as a pathway for return on investment, which [could] be huge,” McCune said. Intellia, a former Gates grantee, is in the preclinical stages of developing an in vivo CRISPR treatment for SCD, company spokesperson Ian Karp wrote in an email to BioSpace. “The benefit of a one-time treatment certainly has applicability to patients across the globe,” he said. “Additionally, our technology platform is modular, such that we do hope to leverage it across multiple indications / diseases. Oftentimes the only change we need to make from one investigational product to the next (particularly when targeting the same cell type and edit type) is in the targeting region of the guide RNA which serves to direct the CRISPR machinery to the gene of interest.” Similarly, Christine Silverstein, chief financial officer at Excision BioTherapeutics (which has not received Gates funding), said that the technology behind the company’s candidate CRISPR HIV treatment, the Fast Tracked EBT-101, may be applied to other chronic viral infectious diseases including herpes and hepatitis B. “In fact, our work in HIV is setting the foundation for advancements of Excision’s pipeline which unites next-generation CRISPR nucleases with a novel, multiplexed gene editing approach to develop potentially curative therapies,” she said in a statement. But success is by no means assured. Despite the current excitement over CRISPR, hurdles to its therapeutic use remain, including not-insignificant safety concerns, and safety issues have also cropped up with other gene therapies. The Gates Foundation itself is hedging its bets, working in parallel to drive the development of a therapeutic vaccine for HIV. Still, McCune is dreaming big. Even for conditions where effective treatments exist, these sorts of in vivo treatments “might be something that takes pills off the shelves and sets the course for a different kind of medicine.” Shawna Williams is a senior editor at BioSpace. She can be reached at shawna.williams@biospace.com or on LinkedIn.

Excision reported positive safety and biodistribution data to 48 weeks in the first-in-human Phase 1/2 clinical evaluation of EBT-101 No serious adverse events or dose-limiting toxicities were seen in any trial participant EBT-101 was detected in blood in all participants SAN FRANCISCO, Oct. 25, 2023 (GLOBE NEWSWIRE) -- Excision BioTherapeutics Inc., a clinical-stage biotechnology company developing CRISPR-based therapies to cure viral infectious diseases, today announced positive safety data from the first dose cohort in its first-in-human Phase 1/2 trial to assess safety and pharmacodynamics of EBT-101. EBT-101 is a dual-guide, CRISPR-based investigational gene therapy for the treatment of human immunodeficiency virus type 1 (HIV-1). The data was presented at the European Society for Gene & Cell Therapy annual meeting on October 25, 2023 in Brussels, Belgium. “Excision is dedicated to developing curative, CRISPR-based therapies for people with infectious disease,” said Daniel Dornbusch, Chief Executive Officer of Excision. “EBT-101 is a CRISPR-based gene therapy being tested as a potential functional cure for HIV. We believe that sharing this initial safety and biodistribution data is important for the HIV/AIDS community, the larger infectious disease community, and for gene therapies in development for other indications.” William Kennedy, M.D., SVP of Clinical Development at Excision commented, “Establishing the safety and biodistribution of EBT-101 is an important first step in the clinical program. Treatment with EBT-101 resulted in no serious adverse events or dose limiting toxicities in the first three participants, and all reported adverse events were mild and reversible. Excision was also able to demonstrate positive biodistribution of the product candidate at this dose level. These initial observations provide important clinical data that support the advancement of the EBT-101-001 trial to the next dosing cohort.” Details of the Abstract and Presentation: Title: First-in-human trial of systemic CRISPR-Cas9 multiplex gene therapy for functional cure of HIV Abstract: OR31 Presenter: Dr. Rachel Presti, Washington University St. Louis School of Medicine Date/Time: Wednesday, October 25, 2023, 14:30-16:30 pm (CEST) EBT-101 is a CRISPR-based therapy being developed as a potential cure for HIV – EBT-101 is being developed as a potential cure for HIV-1 by targeting latently integrated proviral HIV DNA. Latency is a barrier to curing HIV since antiretroviral therapies (ART) do not eliminate latent HIV. Excision uses a multiplexed and in vivo CRISPR-based gene editing approach to excise large segments of latently integrated proviral HIV DNA. All participants in Cohort A (n=3) have been safely dosed – Initial results, as reported by Excision, indicate no serious adverse events or dose limiting toxicities. Although four mild (Grade 1) adverse events (AEs) possibly or definitely related to EBT-101 were observed in the first three participants, all reversed without intervention. Across the Cohort, there were no withdrawals during IV administration, no infusion-related reactions, and no complement-mediated toxicity. Transient and reversible transaminase elevations were observed in two of the three participants. EBT-101 is detectable in blood at 4 weeks in every participant – Peripheral exposure has been achieved with a single dose of EBT-101 at the first dose level being evaluated in the study (9.0x1011 vg/kg). Excision observed no evidence of horizontal transmission of gene vector shedding of EBT-101 in two tissue compartments associated with male reproductive function. Data supports dose escalation to Cohort B and further development of EBT-101 – Excision plans to dose escalate to its next dose level (3.0x1012 vg/kg) in Q4 2023 and present additional data in 2024. About EBT-101 EBT-101 is a first-in-class in vivo CRISPR-based therapeutic designed to cure HIV infection after a single intravenous infusion. EBT-101 employs an adeno-associated virus (AAV) to deliver a CRISPR nuclease and two guide RNAs. By targeting multiple sites in the HIV genome, EBT-101 has been shown to remove large sections of HIV proviral DNA in preclinical studies, thereby rendering HIV incapable of replication. The FDA granted Fast Track designation to EBT-101 in 2023. About the EBT-101 Clinical Program The EBT-101-001 Phase 1/2 trial is an open-label, multi-center, single ascending dose study designed to evaluate the safety, tolerability, biodistribution and pharmacodynamics of EBT-101 in approximately nine participants with HIV-1 with an undetectable viral load on antiretroviral therapy. Preliminary efficacy assessments will also be conducted. Participants in EBT-101-001 will be followed for 48 weeks post EBT-101 administration. All eligible participants will be assessed for sustained viral suppression off their background ART, in an analytical treatment interruption (ATI) starting at Week 12. After EBT-101-001, participants will be enrolled in a long-term follow up study, EBT-101-002. For more information, see ClinicalTrials.gov identifiers NCT05144386 (Phase 1/2 trial) and NCT05143307 (long-term follow up study). The EBT-101 Phase 1/2 clinical trial is supported by a grant from the California Institute for Regenerative Medicine (CIRM). For more information on CIRM go to . About Excision BioTherapeutics, Inc. Excision BioTherapeutics, Inc. is a clinical-stage biotechnology company developing CRISPR-based therapies as potential cures for viral infectious diseases. EBT-101, the Company’s lead program, is an in vivo CRISPR-based therapeutic designed to cure HIV infection after a single intravenous infusion. Excision’s pipeline unites next-generation CRISPR nucleases with a novel gene editing approach to develop curative therapies for Herpes virus, Hepatitis B virus and JC virus, which causes PML. Excision’s foundational technologies were developed in the laboratories of Dr. Kamel Khalili at Temple University and Dr. Jennifer Doudna at the University of California, Berkeley. For more information, please visit . Contact: Investors John Fraunces LifeSci Advisors 917-355-2395 jfraunces@lifesciadvisors.com Media Shira Derasmo Cuttlefish Communications 917-280-2497 shira@cuttlefishpr.com