LEXINGTON, Mass.—Shire PLC has further expanded itsportfolio of orphan disease therapies with the signing of an agreement toacquire privately held Lotus Tissue Repair Inc., a biotechnology companydeveloping the first and only protein replacement for the treatment of theorphan disease dystrophic epidermolysis bullosa (DEB). Currently, no approvedtreatment options exist for the disease other than palliative care.
Though no specific details were released, the acquisitionconsists of an upfront payment as well as certain additional payments ifspecified safety and development milestones are met. The acquisition is subjectto customary government approvals.
Epidermolysis bullosa (EB) is a set of rare genetic diseasescharacterized by extremely fragile skin, and patients suffer recurring blisterformation from even minor amounts of friction or trauma. Of these diseases, DEBis one of the more severe, and in extreme cases of DEB, patients may alsosuffer internal blistering of the mouth, esophagus, upper airway, lowergastrointestinal tract and genitourinary tract. In the recessive form of thedisease, severe blistering and scarring occurs on the hands, feet and joints.By the time a patient reaches their 20s or 30s, DEB leads to the development ofaggressive squamous cell carcinomas in areas of chronic wounding, and theseoften metastasize and lead to death. One of the primary causes of DEB is thedysfunction or deficiency of type VII collagen (C7).
Dr. Philip J. Vickers, global head of research anddevelopment at Shire Human Genetic Therapies (HGT), notes that the globalincidence of DEB is roughly one per million, for an approximate total of 1,275people with the recessive form of DEB and more than 200 with the dominant formof the disease.
"DEB is one the most devastating orphan diseases, severelyimpacting the lives of patients and their families, many of whom have few or notreatment options other than palliative care," said Vickers in a press release."rC7 protein replacement therapy has the potential to provide a first-in-classdisease-modifying treatment for these children. We plan to apply our provenability to develop protein replacement therapies for rare genetic diseases toprogress rC7 as a possible groundbreaking treatment that offers hope topatients with DEB."
Lotus Tissue Repair's lead product candidate is aproprietary recombinant form of C7 (rC7), an intravenous protein replacementtherapy, for which Shire's HGT business will take over further development. Thecompound is in late preclinical development, and preclinical findings show thatas a protein replacement therapy, rC7 is potent, long-lasting and specificallyretained in the skin after intravenous injection. The treatment complementsShire's own existing work in EB, which includes ABH001, a regenerative medicineproduct Shire is investigating as a dermal substitute therapy for the treatmentof non-healing wounds in EB patients.
"This acquisition of Lotus Tissue Repair by Shire furtherunderscores the potential of this proprietary rC7 technology to dramaticallychange the treatment landscape for DEB patients and their families," Dr. Markde Souza, founding CEO of Lotus Tissue Repair, said in a statement. "We arethrilled that this program will become part of the innovative pipeline at Shireand the company's growing commitment to this patient community."
Following the acquisition, Vickers notes that de Souza willjoin Shire's HGT team at the Lexington campus as a consultant, adding thatShire "will be engaging additional consultants who were key to the progressmade by Lotus."
"Shire Regenerative Medicine has experience focusing ondeveloping and delivering solutions that support the body's natural healingprocess, and will use this expertise to develop ABH001 as a skin substitute forEB," says Vickers. "At HGT, we are approaching the treatment of [DEB] from acomplementary angle as an intravenous protein replacement, with rC7 as apotential treatment for the systemic manifestations of the disease. Thisindication leverages our proven protein replacement expertise and is alignedwith the HGT focus on the orphan disease space. In addition to scientificsynergies, we anticipate that the cross-business unit focus on EB will lead tooperational synergies, including coordinated links with patient associationsand centers of excellence."
Shire in RNA researchdeal with Germany's Ethris
MUNICH, Germany—Shire also announced in early January thathas entered into a research-based alliance with Ethris GmbH that will focus onthe development and commercialization of novel RNA-based therapeutics.
Ethris and its co-founders, Dr. Carsten Rudolph and Prof.Christian Plank, have developed a novel RNA modification technology thatcreates Stable and Non-Immunogenic Messenger RNA (SNIM-RNA) molecules that areideally suited for use in protein replacement therapies to treat monogenicgenetic diseases.
"We are delighted to extend our existing collaboration withShire that may bring novel therapeutics to patients suffering diseases withsignificant unmet medical need. We aim to provide significant numbers ofpatients with new therapeutic alternatives that may provide a lasting solutionto their disease," stated Rudolph, who is CEO and co-founder of Ethris.
Financial details of the alliance were not disclosed.