LEXINGTON, Mass.—Targeted toward treating and curing cancer and rare diseases, high-tech, fast-paced, next-generation genetics company Homology Medicines Inc. burst onto the scene after closing a $43.5 million Series A preferred stock financing co-led by 5AM Ventures and ARCH Venture Partners. The March 2015 startup announced May 2 that it was investing an initial $23 million toward treating patients with rare diseases.
Kush Parmar, Homology board member and 5AM Ventures managing partner, contends Homology’s technology is faster and smarter than other firms competing for gene therapy space. Homology’s ability to attract top management, who over many years have "gained scientific and practical knowledge of the complexities of developing treatments for rare genetic diseases, is a testament to the strength of our technology platform,” Parmar stated in a press release.
Homology “has an aggressive development plan and a significant opportunity to leapfrog current strategies in gene therapy and gene editing as it builds an expansive and high-value clinical pipeline,” Parmar added. “We see potential that’s enormous.”
The company and its investors believe they can replace faulty, disease-causing genes with healthy ones without the procedure backfiring and causing safety problems—a fear that looms over the development of other genetic surgery methods.
Dr. Arthur Tzianabos, president and CEO of Homology, stated, “It is rare to find cutting-edge science that takes a fundamentally new approach placed in the hands of experts who have worked together as a team, before, to translate new technologies into treatments targeting the underlying cause of serious genetic diseases.”
“We are convinced that this single technology platform, which enables in-vivo editing by efficient gene transfer, has broad, unmatched capabilities,” Tzianabos said, and he tells DDNews that 5AM “has invested in the gene therapy space before, and has been searching for a while for the next game-changing technology that could transform the field—not just to treat genetic diseases, but to actually cure rare genetic diseases.”
Homology’s “proprietary technology is truly unique,” Tzianabos said. “And the team that is driving this technology forward has worked together in the past to translate new science/technologies into new therapies for rare disease … taking it all the way from concept into development through treatments for patients.”
Homology’s “ability to translate the breakthrough science, select the right indications, know how to develop therapies for rare diseases—all should facilitate a rapid path to patients who are in desperate need for new solutions,” he says.
“Also, we know homologous recombination happens in nature,” Tzianabos says. “Our scientific founder discovered a whole new family of human-derived AAVs (human-derived so they should not have the immunity challenges seen with other types of AAVs). Our AAVs induce this natural process of homologous recombination for both gene delivery and editing in vivo (in the body) using a single technology platform. Other approaches are ex vivo and employ multiple technologies."
Unlike other approaches, “our next-generation genome editing is not dependent on our therapeutic delivering a non-human nuclease,” Tzianabos says. “Importantly, because we are using natural cellular recombination mechanisms, we are able to induce high-precision, efficient, on-target editing. Approaches that use a double-stranded break induce the cell to fix the break by any means possible, and therefore are likely to be more error-prone."
“This homologous recombination mechanism we harness is the same mechanism that the body uses naturally to fix/repair errors during cell replication,” he says. “This mechanism is also the basis for the evolution/generation of diversity.”
As for rare diseases, Homology is likely to initially focus on blood disorders.
“We are assessing our initial indications now and moving quickly into development,” Tzianabos says.
Steven Gillis, managing director with ARCH Venture Partners, stated, “As a scientist and investor, I have evaluated many breakthrough technologies in this field, and I believe Homology’s technology platform is unique in its ability to leverage naturally occurring genetic mechanisms to both treat and correct diseases in vivo.”
“I look forward to helping Homology lead the next-generation gene editing technology that could result in new curative medicines for life-threatening diseases,” Gillis added. “Homologous recombination is a natural genetic mechanism of humans and other biological systems that allows DNA sequences, which are very similar and close in sequence, to switch from one chromosome to another—or enabling organisms to transfer.”
Homology obtained an exclusive worldwide license to its technology platform, based on the pioneering research of Dr. Saswati Chatterjee in the Department of Surgery at the Beckman Research Institute of City of Hope, based in Duarte, Calif. Chatterjee is also co-founder and chair of Homology’s scientific advisory board.
Chatterjee and her team led the first adeno-associated virus (AAV) vector-mediated gene transfer studies into human hematopoietic stem cells and subsequently identified and isolated a series of naturally occurring AAVs from human CD34+ cells.
The big difference between Chatterjee’s AAVs and others often used in gene therapy programs developed or owned by companies, such as RegenXBio, is their ability to transfer DNA to their targets and cause homologous recombination.
Founded in 2002, 5AM Ventures invests in next-generation life-sciences companies. With $685 million under management, 5AM has invested in over 55 early-stage companies, and its successful realizations include DVS Sciences (acquired by Fluidigm), Envoy Therapeutics (acquired by Takeda), Flexion Therapeutics, Ikaria (acquired by Mallinckrodt), Ilypsa (acquired by Amgen), Incline Therapeutics (acquired by The Medicines Company), Marcadia (acquired by Roche), Novira (acquired by J&J), Pearl Therapeutics (acquired by AstraZeneca) and Relypsa.
ARCH Venture Partners invests in the development of seed and early-stage advanced technology companies that have the potential to grow rapidly into successful businesses. ARCH invests primarily in companies that they co-found with leading scientists and entrepreneurs, concentrating on bringing to market disruptive innovations in life sciences, physical sciences and information technology.