Industry News July 2020

Key words:

• AAV
• blood–brain barrier
• gene delivery
• Industry update

Company news

$23 billion investment for ophthalmology pipeline development for Artic Vision

Artic Vision (Shanghai, China), a biotechnology company, announced on 13 July 2020 that they had secured a $32 million Series A investment, to allow for the development of their ophthalmology pipeline. The financing will help progress clinical trials in China for fARVN001. ARVN001 is formulated as a suspension of the active triamcinolone acetonide. This formulation has been designed for delivery via suprachoroidal space administration. The initial indication under clinical evaluation will be macular edema associated with uveitis. The delivery of the active is achieved by using a proprietary suprachoroidal space Microinjector™.

Artic Vision licensed ARVN001 from Clearside Biomedical (GA, USA) and has exclusive rights to develop and commercialize the product in China and related regions [1].

Sorrel Medical opens manufacturing facility for wearable drug delivery & partners with major global pharmaceutical manufacturer

In two separate announcements in July Sorrell Medical (Netanya, Israel) disclosed a new partnership with a major pharmaceutical manufacture and the opening of a new manufacturing facility for its wearable drug delivery platform.

Announcing the opening of the new facility that includes an ISO class 7 cleanroom, an ICQ laboratory and a warehouse, Bentsi Algazi (Sorrell Medical) said “As Sorrel continues to grow, this new facility will enable us to support global pharmaceutical and biotechnology partners to bring next-generation drug delivery solutions to patients”.

Sorrel’s wearable drug delivery platform is digitally enabled and is designed for subcutaneous delivery of injectable drugs, biologics and biosimilars. The company also announced in July that it had partnered with an undisclosed major global manufacturer to facilitate the delivery of a number of therapeutic molecules across a range of configurations for their platform [2,3].

Harvard announce the launch of Vesigen Therapeutics

It was announced on 23 July 2020, that Vesigen Therapeutics (MA, USA) was being formed as a spin out from Harvard University (MA, USA). The company will focus on the development of delivery platforms for therapeutics including large proteins, such as gene-editing complexes and RNA molecules. The new company was financed by $28.5 million in Series A investment. This enabled the licensing of drug-delivery technologies developed in Quan Lu’s labs in the Harvard Chan School (MA, USA). The delivery vehicles developed are based on Lu’s arrestin domain containing protein 1 (ARRDC1)-mediated micro-vesicles. These micro-vesicles have been engineered to allow for the packaging and intracellular delivery of clinically relevant macromolecules.

Initially the company intends to focus on the development of novel therapeutics for the treatment of neurological diseases and in the areas of oncology and ophthalmology. It also intends to offer the platform for licensing in other companies and other therapeutic areas [4].

Avanti Polar Lipids agrees to be acquired by Croda

Avanti Polar (AL, USA) announced on 6 July 2020 that it had agreed to be acquired by the British speciality chemicals company, Croda International (Snaith, UK). Employing over 150 people at its facility in Alabama the company’s focus is the development and production of lipids for use as drug delivery vehicles for low-bioavailability actives and mRNA vaccines.

Discussing the acquisition, Steve Foots (Croda) stated “We have long admired the Avanti team for their deep scientific know-how and are already working together on high-potential commercial opportunities. With their exciting drug delivery technologies, Avanti is a market leader in a high growth niche of the healthcare market, serving over 3000 customers globally. Bringing Avanti’s best-in-class expertise into Croda also significantly enhances our presence across the pharma product lifecycle, including early stage R&D, clinical trials, analysis and formulation. I am confident that Avanti will prove transformative to the capabilities and performance of our Life Sciences sector” [5].

Collaborations & agreements

Princeton & Genetech partner to develop novel drug-delivery formulations

On 31 July 2020, Princeton University (NJ, USA) announced a new partnership with the biotechnology company Genentech (CA, USA). The stated aim of this partnership is to allow for a funding of up to five projects in areas including, vaccine delivery and immunology. The total funding for these projects is expected to be $65 million over 2 years.

The projects being funded include one supervised by Robert Prud’homme and Haw Yang (Princeton University), which explores the possibility of exploiting endosomal escape mechanisms for vaccine delivery.

Princeton have already established similar partnerships with other pharma/biopharma companies including Bristol-Myers Squibb (NY, USA), Celgene (NJ, USA), Janssen (Beerse, Belgium) and Merck (NJ, USA) [6].

Approvals & regulatory updates

Foresee submits New Drug Application for leuprolide depot

Foresee Pharmaceuticals (Taipei, Taiwan) announced on 27 July 2020 that it had submitted an New Drug Application for its 6-month depot leuprolide mesylate product, Camcevi™. The intended indication for the depot is for the palliative treatment of advanced prostate cancer. The submission follows a successful Phase III study in 137 patients with advanced prostate cancer and includes additional device design verification data that had been requested by the US FDA in 2019.

In 2019, Foresee Pharmaceuticals signed an exclusive license agreement for the commercialization of Camcevi with Accord Healthcare (Barnstable, UK) globally excluding USA, mainland China, Japan and a number of territories covered by previous agreements. Under the terms of this agreement, Foresee will receive $86 million, a combination of upfront, regulatory and sales milestone payments and Accord Healthcare will cover the commercialization costs [7].

Positive CHMP opinion for Heron Therapeutics’ Zynrelief

Heron Therapeutics (CA, USA) announced on 24 July 2020 that it had received a positive opinion for its controlled relief pain medication, Zynrelief, from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP). A final decision on marketing approval is expected from the European Medicines Agency by the end of the year. The positive opinion received was based on two Phase III trials that demonstrated a significant reduction in both postoperative pain and opioid pain relief. The CHMP recommendation is for treatment in adults with postoperative pain for small to medium-sized wounds.

Zynrelief is formulated as a fixed-dose combination of the bupivacaine and a low dose of meloxicam, utilizing Heron’s proprietary Biochronomer^® polymer delivery system, that allows for a controlled release of the actives over approximately 72 h.

Biochronomer is Heron’s proprietary delivery platform that consists of a tri(ethylene glycol) poly(orthoester) polymeric system designed to deliver, by a single subcutaneous injection, a sustained release dose of the active(s) [8].

Clinical trials

Positive Phase III data for Roche’s ocular delivery system

On 22 July 2020, Roche (Basel, Switzerland) announced data from its Phase III Archway study. The study enrolled 418 patients in total and evaluated Roche’s Port Delivery System (PDS) with ranibizumab for the treatment of neovascular age-related macular degeneration (AMD). The results presented indicated that 98.4% of patients receiving treatment via the PDS were able to go 6 months without requiring further treatment. Post this 6-month period, these patients achieved vision outcomes equivalent to patients treated using the current standard of care; monthly ocular injections of ranibizumab.

Roche’s PDS is a permanent refillable eye implant, which has been designed to be the size of a rice grain. It facilitates continuous delivery of a customized formulation of ranibizumab; a monoclonal antibody fragment approved for the treatment of neovascular or wet AMD into the eye over a period of months.

Globally it is estimated that there are 17 million people living with wet AMD and it is the leading cause of vision loss in those aged of 60 or over [9].

SINOMED completes Phase III follow-up for its drug-eluting stent

On 13 July 2020, SINOMED (Tianjin, China) announced the completion of a 1-year follow-up to its PIONEER-III, Phase III global trial. This trial was designed to evaluate BuMA Supreme Drug-Eluting Coronary Stent. SINOMED intends to submit the data to the FDA as well as the Japanese Pharmaceuticals and Medical Devices Agency for device approval in the near future.

The randomized trial’s end point is target lesion failure at 12 months. The 1631 patients enrolled in the trial at over 74 sites will be followed up for 5 years post study enrollment, as part of the clinical trial. The BuMA Supreme has already achieved CE approval and has been designed with a proprietary biodegradable polymer coating technology to facilitate a quicker return of normal cellular functionality and a novel release mechanism for the active, sirolimus, which the company claims out performs competitor drug-eluting coronary stent’s [10].

Oramed to commence Phase III studies for oral insulin

On 15 July 2020, Oramed (NY, USA) reported a successful meeting where Phase II data was presented to and discussed with the FDA for its oral insulin product, ORMD-0801. According to the company, the FDA has outlined its expectations for the design of the proposed Phase III trials and also discussed the proposed submission of a Biologics License Application. Based on the feedback from the FDA, the company propose to concurrently run two Phase III trials.

Oramed’s propriety delivery platform, employed in ORMD-0801, is known as the Protein Oral Delivery (POD™) technology. The key advantages of Oramed’s delivery platform is that it can protect orally delivered proteins from enzymatic degradation within the gastrointestinal tract and it is also designed to enhance their absorption across the intestinal wall by encapsulation of the active and inclusion of specialized protease inhibitors and absorption enhancers in the formulation. Separately Oramed is developing an oral glucagon-like peptide-1 (GLP-1) analogue formulation, termed ORMD-0901 [11].

After COVID-19 related pause Abeona recommences gene therapy clinical trial

Abeona Therapeutics (NY, USA) provided a clinical programme update on 18 July 2020. This update reported Abeona’s restart of patient enrollment for its pivotal Phase III VIITAL™ study of EB-101. This study was paused in March due to the COVID-19 outbreak. EB-101 is Abeona’s autologous cell therapy candidate in late-stage clinical evaluation for the treatment of recessive dystrophic epidermolysis bullosa. Additionally, the company provided an update on the clinical programme, mucopolysaccharidosis (MPS) III, for its adeno-associated virus (AAV)-based gene therapies, ABO-102 and ABO-101. Both candidates are for the treatment of Sanfilippo syndrome type A in children. The company has reported that these trials have continued during the COVID-19 crisis given the urgent need to treat children as quickly as possible following diagnosis.

Joao Siffert (Abeona Therapeutics), commented on the update “We have worked closely with sites in our MPS III clinical studies to continue to enroll patients given the urgent need to treat children with Sanfilippo syndrome as early as possible. We are encouraged by the number of new pre-screened patients that may meet enrollment criteria and could allow dosing in the coming weeks. We also hope to resume on-site follow-up study visits that include neurocognitive assessments of already enrolled patients” [12].

Entera Bio reports Phase II clinical trial update for osteoporosis drug

On 7 July 2020, Entera Bio (Jerusalem, Israel) announced that following the analysis of the interim Phase II biomarker and safety data for its oral Parathyroid Hormone 1–34 (PTH 1–34) product, EB613, it was applying for an amendment to the clinical trial protocol, to allow for the evaluation of a higher dose of EB613. Currently there are 106 patients enrolled and the company have indicated that it intends to enroll 160 patients, including the proposed additional high-dose group. This trial is investigating EB613 in postmenopausal female patients with osteoporosis, or low bone mass density.

Entera’s proprietary drug delivery platform facilitates the oral delivery of macromolecules by both increasing oral bioavailability and reducing the degradation of the active, with the aim of decreasing the variability associated with the oral administration of macromolecular therapeutics [13].

REGENXBIO provides update on its clinical programmes

REGENXBIO (MD, USD) provided a clinical programme update on 8 July 2020 for its lead candidates, RGX111 and RGX121. RGX111 is a product candidate for the treatment of MPS I and RGX121 is undergoing clinical investigation for the treatment of MPS I). Both employ an adeno-associated virus vector (AAV9) to deliver a genetic payload, the α-l-iduronidase (IDUA) gene in the case of RGX111 and human iduronate-2-sulfatase (IDS) gene in the case of RGX121. It is proposed that the delivery of the enzymes that are deficient within cells in the CNS of those suffering from MPSI/II, has the potential to facilitate both permanent source of secreted IDUA/IDS beyond the blood–brain barrier. It is also proposed that this delivery mechanism could allow for delivery to the brain, which could prevent cognitive deficits in the case of RGX11I. Both candidates have received orphan drug product/fast-track designation by the FDA.

Discussing the RGXIII clinical program the company reported what it termed ‘encouraging data’ under a single-patient investigator-initiated Investigational New Drug application. In the case of RGX121, the company reported that it had completed dosing of three patients in Cohort 2 of the Phase I/II study for the treatment of MPS II. The company stated that enrollment of this cohort is now completed, and initial reports indicate that the dosage was well tolerated with no serious adverse events reported. The company indicated that additional data from both study cohorts would be available later this year [14].

Hoag implants, first DBS with BrainSense technology for Parkinson’s disease

Hoag Memorial Hospital Presbyterian (CA, USA) announced on 20 July 2020 that it had carried out its first implant surgery of the recently FDA-approved Percept™ PC deep-brain stimulation (DBS) system in a patient with Parkinson’s disease. Percept is Medtronic’s (Dublin, Ireland) device that allows for patient-specific brain signal monitoring and can allow for optimization of treatment for patients with neurological disorders, such as Parkinson’s disease and epilepsy.

The implant was approved in early July for patients with Parkinson’s disease and has been designed to allow for a more individualized approach for using DBS therapy in patients with Parkinson’s disease and related disorders. Percept PC deep-brain stimulation is the first DBS system approved to be capable of sensing and recording brain signals as a delivered therapy and it is hoped that this will help doctors to meet a patients therapeutic needs more precisely [15,16].

Arctutus & Duke to commence Phase I/II clinical trial for COVID-19 vaccine

The biotechnology company, Arcturus Therapeutics (CA, USA) announced on 21 July 2020 that it had received approval from the Singapore Health Sciences Authority for a Phase I clinical trial for its COVID-19 vaccine candidate, LUNAR-COV19. Acturus plan to co-develop the vaccine with Duke-NUS Medical School (Singapore). The vaccine candidate will employ Arcturus’ STARR™ and LUNAR^® lipid-mediated delivery technologies. It was reported that 100% seroconversion for anti-SARS-CoV-2 neutralizing antibodies was observed.

Discussing the preclinical data and the proposed clinical trial, Ooi Eng Eong (Duke-NUS Medical School, Singapore) said, “Preclinical studies on LUNAR-COV19 have shown very promising findings, including the possibility that a single dose of this vaccine may be sufficient to trigger robust and durable immune responses against SARS-CoV-2. We are very eager to start the first-in-human clinical trial here in Singapore and advance LUNAR-COV19 on its journey to becoming a potential commercial vaccine” [17].

Spark Therapeutics updates Phase I/II clinical trials in Haemophilia A

Spark Therapeutics (PA, USA) provided a clinical update on its gene-therapy candidate, SPK-8011. This therapeutic utilizes Spark’s proprietary AAV vector, the AAV-LK03 capsid, for the delivery of the human factor VIII gene to treat Haemophilia A. Reporting on the update Federico Mingozzi (Spark Therapeutics) stated, “We are very encouraged by these interim data that continue to show an acceptable safety profile and a substantial reduction in bleeds for more than 2 years of observation on average, with one participant being observed for more than 3 years. Our focus is on optimizing the dose and immunomodulatory regimen before moving to a Phase III clinical study that falls in line with our strategy to progress a Haemophilia A gene therapy that, at the lowest effective dose and the optimal immunomodulatory regimen, demonstrates safety, predictability, efficacy and durability”.

Data reported from the 14 participants dosed, indicated a rapid clearance (within 2 weeks post-vector administration) of the vector from bodily fluids analyzed including, urine, serum, saliva and semen. Additionally, it was reported that the vector was not detectable in peripheral blood mononuclear cells sampled by 6 weeks post administration of the vector in all participants [18].

Early stage development

MIT develop model to improve microparticulate delivery in injectables

Massachusetts Institute of Technology (MIT, MA, USA) scientists, with funding from the Bill and Melinda Gates Foundation, the National Cancer Institute and the National Institutes of Health have conducted research into developing a novel computational model that could prevent microparticle clogging when delivering microparticles via an injectable formulation. The researchers claim that this novel model can be employed to produce a sixfold increase in the percentage of microparticles that can be successfully injected. The researchers further claim that this could have very significant applicability in the delivery of novel cancer immune-therapeutics [19].

Patents

Evox expands exosome patent portfolio

Evox Therapeutics (Oxford, UK) announced on 15 July 2020 that it had been granted a new patent by the United States Patent and Trademark Office, US Patent 10,704,047. This patent further strengthens Evox’s exosome patent portfolio and the company claims it will offer broad coverage for formulations of exosomes, which can be loaded by electroporation for payloads including nucleic acid-based therapeutics. The company’s engineered exosomes technology platform has been trademarked as DeliverEX™ [20].

ARS Pharmaceutical announces a new patent for its epinephrine nasal spray

In July, ARS Pharmaceuticals (CA, USA) reported the issuance by the United States Patent and Trademark Office of a second patent for its lead clinical candidate, ARS-1. ARS-1 is formulated as a low dose intranasal spray for epinephrine. ARS-1 employs a proprietary excipient, Intravail^®, owned by Neutrelis Inc. (CA, USA), which enhances mucosal absorption via both transcelluar and paracelluar mechanisms. The patent, US Patent No. 10,682,414 relates to methods for the use and intranasal administration of epinephrine in the dose range of 0.1–2.4 mg [21].

Summary

The present industry update covers the period July 2020, with information sourced primarily from company press releases, scientific literature and various news websites. The effect of the COVID-19 pandemic could be observed both in the pivoting of some development/clinical programmes to treat symptoms of this viral infection/development of vaccines to prevent it and the impact it is having on the global pharmaceutical industry. This month saw Foresee Pharmaceuticals indicate that it would file an New Drug Application for Camcevi (a leuprolide depot) and a positive CHMP opinion for Heron Therapeutics’ Zynrelief. In company news the lipid-development company Avanti Polar Lipids announced that it was to be acquired by UK-based Croda International. July 2020 also saw a number of companies reporting positive clinical data for therapeutics that relied on a variety of therapeutic delivery strategies, including Oramed, Entera Bio and Abeona.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.