Orchard Therapeutics announces historic agreement making Libmeldy available by NHS England for MLD patients

On February 3, 2022 Orchard Therapeutics (Nasdaq: ORTX), a global gene therapy leader, reported it has reached an agreement with the National Health Service (NHS) that enables access to Libmeldy (atidarsagene autotemcel) for all children with metachromatic leukodystrophy (MLD) in England and Wales who fall within the scope of the European marketing authorization (Press release, UCLB, FEB 3, 2022, View Source [SID1234607796]). The agreement coincides with publication of the positive National Institute for Health and Care Excellence’s (NICE) final evaluation determination, which recognized the clinical impact and economic benefit of Libmeldy according to the institute’s Highly Specialized Technologies (HST) process. In addition, the company announced the first two commercially treated patients in Germany and France under reimbursement mechanisms for early access. A third patient from the Middle East was referred for international reimbursed treatment abroad in Italy.

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"Today’s landmark agreement with NHS England follows a thoughtful and comprehensive value assessment by NICE and represents a major milestone for the MLD community, Orchard, and the entire field of HSC gene therapy," said Professor Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. "We are delighted that NICE and NHS England have recognized the transformational clinical impact and significant economic value of Libmeldy for eligible MLD patients, and thank the leading clinicians and advocates involved for their tireless engagement throughout the process. A deep body of evidence now points to the potential for durable effects in HSC gene therapy for certain severe genetic diseases including MLD. I am grateful for the opportunity we have at Orchard to commercially scale the reach of our therapeutic approach for patients in need—starting with MLD."

MLD is a rare, rapidly progressing, irreversible and fatal genetic disorder caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of fats called sulfatides in the brain, peripheral nerves, and other areas of the body, including the liver, gallbladder and kidneys. Over time, the nervous system is damaged, and children with MLD experience neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. In its most severe form, children quickly lose the ability to walk, talk and interact with the world around them. The majority of these children pass away before adolescence. Libmeldy is the only one-time gene therapy intended to correct the underlying cause of MLD in eligible patients approved in Europe. In clinical studies, Libmeldy resulted in sustained, clinically relevant benefits in children with early-onset MLD by preserving cognitive function and motor development in most patients.

"MLD causes catastrophic physical suffering for affected children and places immense physical, emotional and financial burden on their families," said Georgina Morton, chairperson of ArchAngel MLD Trust. "Previously, there was a dearth of treatment options for this condition, which was mainly managed using supportive care. Our community is deeply appreciative of the NHS and NICE for recognizing the significant medical need in MLD and paving the way for eligible children in England and Wales to now have access to this important therapy. As advocates we are now turning our sights to advancing newborn screening for MLD in order to help as many future MLD affected patients as possible."

Updates on Commercial Momentum in Europe
Since the European Commission approval of Libmeldy, Orchard Therapeutics has continued to build its commercial infrastructure in the region to support patient identification and treatment efforts. Recently, the first two commercially treated patients were infused with Libmeldy at Tübingen University Hospital and the Hôpital Debré in Paris, two of the treatment centers qualified to administer the therapy. Both patients are being treated under reimbursed early access arrangements available in the respective countries while final reimbursement negotiations are ongoing with national authorities. In addition, through the company’s commercial partnership with Genpharm, a patient from the Middle East has been identified and referred for reimbursed international treatment abroad at Ospedale San Raffaele in Milan, Italy.

To continue identifying eligible patients in the appropriate treatment window, the company has launched a newborn screening pilot in Germany and is planning additional screening initiatives in other European countries, including Italy, the UK, Spain and France, while it continues to work with its clinical partners to support additional ongoing diagnostic and disease education initiatives throughout the region.

"The early launch momentum we’re experiencing with Libmeldy in Europe is very encouraging and confirms the company’s strategy to focus on areas of significant need where we believe our HSC gene therapy platform approach has distinct therapeutic potential," said Braden Parker, chief commercial officer of Orchard Therapeutics. "We are pleased with the agreement we’ve reached with NHS and are committed to working closely and urgently with governments, health authorities and payers in other European countries to enable access for eligible young children in those localities who may benefit from this therapy. These efforts coincide with the fact that for the first time ever eligible children with MLD have received treatment with Libmeldy in the European commercial setting, with another patient in the process of referral and treatment. Our team has worked diligently alongside our partners to reach this moment. I am incredibly proud of their collective efforts and look forward to the next steps in our company’s commercial journey."

About MLD
MLD is a rare and life-threatening inherited disease of the body’s metabolic system occurring in approximately one in every 100,000 live births. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.i

About Libmeldy / OTL-200
Libmeldy (atidarsagene autotemcel), also known as OTL-200, has been approved by the European Commission for the treatment of MLD in eligible early-onset patients characterized by biallelic mutations in the ARSA gene leading to a reduction of the ARSA enzymatic activity in children with i) late infantile or early juvenile forms, without clinical manifestations of the disease, or ii) the early juvenile form, with early clinical manifestations of the disease, who still have the ability to walk independently and before the onset of cognitive decline. Libmeldy is the first therapy approved for eligible patients with early-onset MLD.

The most common adverse reaction attributed to treatment with Libmeldy was the occurrence of anti-ARSA antibodies. In addition to the risks associated with the gene therapy, treatment with Libmeldy is preceded by other medical interventions, namely bone marrow harvest or peripheral blood mobilization and apheresis, followed by myeloablative conditioning, which carry their own risks. During the clinical studies, the safety profiles of these interventions were consistent with their known safety and tolerability.

For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website.

Libmeldy is approved in the European Union, UK, Iceland, Liechtenstein and Norway. OTL-200 is an investigational therapy in the U.S.

Libmeldy was developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy.

Synaffix Inks $586m Deal with MacroGenics to Enable Next Generation ADCs

On February 3, 2022 Synaffix B.V., a biotechnology company focused on commercializing its clinical-stage platform technology for the development of antibody-drug conjugates (ADCs) with best-in-class therapeutic index, reported it has entered into a technology agreement with MacroGenics, Inc. (Nasdaq: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer (Press release, Synaffix, FEB 3, 2022, View Source [SID1234607674]).

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Under the licensing agreement, MacroGenics will gain access to Synaffix’s clinical stage GlycoConnect antibody conjugation technology, HydraSpace polar spacer technology, as well as select toxSYN linker-payloads (SYNtecan E, SYNeamicin D and SYNeamicin G), each designed to enable ADCs with best-in-class efficacy and tolerability. These will be combined with MacroGenics’ proprietary antibody and bispecific DART antibody platform technologies to generate next generation ADCs.

Under the terms of the agreement, Synaffix will be eligible to receive up to $586 million in payments spanning upfront and milestone payments across three programs plus royalties on commercial sales. The license rights of MacroGenics for each program will be designated as exclusive or non-exclusive to each program’s antibody target (or to the combination of two targets, if bispecific). The first program will commence at signature, with the option to expand the collaboration to a further two programs by March 2023.

MacroGenics will be responsible for research, development, manufacturing and commercialization of the ADCs. At the same time, Synaffix will support MacroGenics’ research activities and be responsible for the manufacturing of components that are specifically related to its proprietary GlycoConnect and HydraSpace technologies and the toxSYN linker-payloads.

Ezio Bonvini, M.D., Chief Scientific Officer of MacroGenics, commented:

"We are delighted to be working with Synaffix to produce next generation ADCs with potentially superior therapeutic properties. The ability to obtain all essential ADC technologies from Synaffix, and easily and rapidly combine those with our antibody-based molecules, will enable us to expand our existing portfolio of ADC product candidates and further strengthen our position in the growing ADC field."
Peter van de Sande, Chief Executive Officer of Synaffix, said:

"The collaboration with MacroGenics is an important milestone for Synaffix as our ADC technology will be deployed for the generation of both monospecific and bispecific ADCs. We are pleased to further expand the use of our technology with another leading biotech company that has deep product development capabilities and a long-term commitment to delivering novel therapies for the treatment of cancer."

Silverback Therapeutics to Participate in the SVB Leerink 11th Annual Global Healthcare Conference

On February 3, 2022 Silverback Therapeutics, Inc. (Nasdaq: SBTX) ("Silverback"), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, reported that Silverback management will participate in the SVB Leerink 11th Annual Global Healthcare Conference from February 14-18, 2022 (Press release, Silverback Therapeutics, FEB 3, 2022, View Source [SID1234607689]).

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Laura Shawver, Ph.D., Silverback’s Chief Executive Officer, and Valerie Odegard, Ph.D., Silverback’s President and Chief Scientific Officer, will participate in a fireside chat on Wednesday, February 16th, 2022, at 1:00 PM ET (10:00 AM PT). The live webcast of the event will be available on Silverback’s Investor Relations website and a replay will be available for 30 days following the event. Members of the Silverback management team will also host investor meetings during the conference.

Avacta Announces Dose Escalation in the Phase I Clinical Study of AVA6000 Pro-doxorubicin

On February 3, 2022 Avacta Group plc (AIM: AVCT), a clinical stage oncology drug company and developer of powerful diagnostics based on its innovative Affimer and pre|CISION platforms, reported that the first-in-human Phase I trial (ALS-6000-101) of AVA6000 Pro-doxorubicin will advance to the next dose cohort following a positive review of the safety data from the dosing of the first cohort (Press release, Avacta, FEB 3, 2022, View Source [SID1234607709]).

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Avacta’s Safety Data Monitoring Committee (SDMC), comprised of clinicians currently recruiting patients, has completed its review of the safety data from the first cohort dosed with AVA6000 at 80mg/m2 in the ongoing Phase I trial. Following this review, the SDMC has recommended that the clinical trial continues as planned and escalates to the next dose of AVA6000 at 120mg/m2.

AVA6000 is a novel form of doxorubicin that has been modified with Avacta’s pre|CISION platform to improve its safety and therapeutic index. Anthracyclines such as doxorubicin, a generic chemotherapy with a market size that is expected to grow to $1.38bn by 20241, are widely used as part of standard of care in several tumour types, but their use is limited by cumulative toxicity. AVA6000 has been designed to limit cell penetration of the drug, and therefore its cell killing effect, until it is specifically activated by fibroblast activation protein α (FAP) which is in high concentration in many solid tumours compared with healthy tissues. The resulting reduced exposure of healthy tissues to active doxorubicin has the potential to significantly increase its therapeutic index by reducing the incidence of adverse effects, including cardiotoxicity and myelosuppression.

Dr Alastair Smith, Chief Executive Officer of Avacta Group, commented: "We are delighted with the SDMC’s recommendation to move on to the next dose of AVA6000 in our dose escalation study following its positive review of the safety data from patients in the first cohort."

"We are very excited by the potential of AVA6000, and the pre|CISION platform more broadly, to deliver ground-breaking and affordable cancer treatments that have the potential to significantly improve patients’ lives."

Press Release: Doxorubicin Market Size is Expected to Reach $1.38 Billion by 2024: Grand View Research, Inc. (23 November 2016)

Takeda quarterly financial report for the quarter ended December 31, 2021

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