Industry update, June 2023

Company News

Stevanato launches on-body drug delivery device

Stevanato Group, an Italian company based in Piombino Dese, announced on 12 June that they had launched Vertiva™, the latest version of their patented on-body delivery system (OBDS). The company claims that this proprietary device is capable of switching between both basal and bolus injections and has been designed to accommodate the subcutaneous delivery of a wide range of therapeutics.

Vertiva contains a single-use pod with a pre-filled and pre-loaded 3 ml cartridge and has been designed with a multi-use controller. A proprietary magnetically coupled drive mechanism is employed to allow for the programmable delivery of small-molecule drugs and biologics. The company intends to leverage their recently announced collaboration with Thermo Fisher Scientific (MA, USA) to market the device.

Speaking at the launch, Steven Kaufman, VP for Drug Delivery Systems at Stevanato Group stated: “The Vertiva™ on-body delivery system supports pharma companies in increasing the accessibility of in-home care and administered treatment options, which can ultimately lead to an improved patient experience. We are excited to be offering this device to the market, as it contributes to further strengthening our integrated capabilities in the drug delivery space. By utilizing a re-usable controller, we work toward greater sustainability and see cost benefits to our customers that use Vertiva™” [1,2].

Lohmann Therapie-Systeme acquires Eitan's Sorrel wearable injection device

It was announced on 8 June that Lohmann Therapie-Systeme AG (Andernach, Germany) had completed its acquisition of the Sorrel wearable injection device business from Eitan Medical Ltd (Netanya, Israel). Financial details of the trade were not disclosed.

The Sorrel device has been designed for the subcutaneous delivery of large-molecule drugs. Its design allows it to be compatible with both vials and cartridges, allowing for the potential delivery of a wide variety of volumes, ranging from 3 to 50 ml. It is anticipated that this acquisition will complement Lohmann Therapie-Systeme's existing drug delivery platform that includes oral thin films, transdermal patches and microarray patches.

Discussing the arrangement, Bas van Buijtenen, CEO of Lohmann Therapie-Systeme, commented: “The acquisition of our new Device Technologies platform catapults LTS into the world of drug delivery for large molecules, and fulfils our mission to bring empowering solutions to patients that rely on cumbersome and expensive therapies requiring in-clinic administration or multiple injections. The Sorrel solutions set a new standard for performance, quality, reliability, and patient convenience in wearable injection devices. The technology is now ready for commercial launch and will accelerate its scale-up within LTS, benefiting from LTS's global reach and reputation” [3].

CD Bioparticles launches new range of PLGA-based drug-delivery systems for in vitro & in vivo applications

On 15 June New York-based CD Bioparticles announced that it had launched a new range of proprietary poly (lactide co-glycolide), PLGA, nanoparticles for use as drug-delivery systems in both in vitro and in vivo applications. Included in the range are a variety of streptavidin-coated PLGA nanoparticles, functionalized PLGA nanoparticles and fluorescently labeled magnetic PLGA nanoparticles. In addition, the company has announced that it can provide additional functionality into the nanoparticles available on their platform by the inclusion of carboxyl and PEGylated groups on the nanoparticle surface [4].

Novo Nordisk to acquire a majority stake in BioCorp

It was announced on 5 June by Novo Nordisk A/S (Bagsværd, Denmark) that it had entered exclusive negotiations to acquire a controlling stake in BIOCORP Production SA (Issoire, France). BIOCORP's key business is the development of innovative medical devices and delivery systems. The two companies have an existing development agreement employing BIOCORP's Mallya, a Bluetooth-enabled device for pen injectors, to be used in conjunction with Novo Nordisk's FlexTouch pen for the treatment of diabetes and other indications.

Discussing the proposed acquisition Marianne Ølholm, Senior Vice President, Devices and Delivery Solutions at Novo Nordisk commented; “Novo Nordisk has strong and established core capabilities within developing, scaling and large-scale manufacturing of innovative injection devices for insulin and other medicines, and we are looking to increase agility to enable faster innovation and development of novel connected devices. We have enjoyed a fruitful collaboration with BIOCORP over the past couple of years, and we hope to be able to welcome the company and its highly skilled workers into Novo Nordisk to complement our in-house efforts within connected delivery solutions and accelerate our ambitions within devices and delivery solutions” [5,6].

Collaborations & agreements

The Centre for Process Innovation to establish a new UK Intracellular Drug Delivery Centre

It was announced on 2 June that the Centre for Process Innovation in partnership with Medicines Discovery Catapult, the University of Strathclyde, the University of Liverpool and Imperial College London is to establish a new center to support RNA therapeutic development. The center will be funded through a £10 million grant from Innovate UK's Transforming Medicines Manufacturing program. The focus will be developing new lipid nanoparticle formulations for therapeutic delivery and facilitating the development of next-generation drug delivery systems. In addition, the new center will also provide workforce training and development [7].

Future Fields & Jenthera Therapeutics to develop novel protein for the delivery of ribonucleoproteins

Jenthera Therapeutics (Québec, Canada) announced on June 13th that it had established a collaboration with Edmonton-based Future Field, a company that has developed a proprietary synthetic biology system to use fruit flies for recombinant protein production. The focus of this collaboration will involve the use of Jenthera's CRISPR-derived in vivo delivery mechanism for protein-based drugs. Jenthera claims its novel direct protein delivery CRISPR platform will eliminate the need for delivery vehicles including viruses, lipids and nanoparticles. The companies anticipate that direct delivery of the ribonucleoprotein will improve safety profiles both in terms of off-target incidence and immunogenicity. Future Fields have developed a proprietary platform, EntoEngine™, which they claim allows for the production of proteins in a more sustainable and cost-effective manner than conventional approaches to biopharmaceutical production techniques.

Speaking at the announcement Philip Roche, PhD, CEO of Jenthera Therapeutics said; “This collaboration with Future Fields reflects our commitment to seeking new and innovative approaches to cost-effectively provide high-quality gene editing biologics at scale, and enable us to advance our sustainability goals. With the EntoEngine™ platform, we can achieve large yields of our novel protein therapeutic, and spool up toward GMP much faster than other cell-based methods. This is integral to our strategy of delivering groundbreaking therapeutics and transforming oncology” [8,9].

Feldan Therapeutics secures $16.5 million funding for clinical development

Feldan Therapeutics (Québec City, Canada) announced on 13 June the initial closing of its series B funding round. Funding achieved of $16.5 million will be used for phase I/II clinical trials of FLD-103, an intralesional treatment against basal cell carcinoma, and to advance its preclinical stage pulmonary program. Feldan has developed a proprietary peptide intracellular delivery technology that it calls the ‘Feldan Shuttle’. Feldan claims this peptide can successfully circumvent endosomal entrapment and facilitate intercellular uptake of a wide variety of therapeutics. Investors in this round of funding include Amgen Ventures and GC Cell (South Korea).

Speaking at the closure of the initial Series B funding round, Ugur Gunaydin, General Manager of Amgen Canada said; “We are delighted that Amgen is investing in this leading Quebec-based biotech company. As one of the world's leading biotechnology companies, Amgen is fundamentally value based and deeply rooted in science and innovation to transform new ideas and discoveries into medicines for patients with serious illnesses. Feldan's novel and unique drug delivery technology is an example of the important innovation coming from Quebec's Life Sciences sector. We are very excited to see this technology's potential expanding in the development of next generation therapies for patients everywhere with unmet medical needs” [10].

Bayer partners with Acuitas for drug delivery technology for gene therapy portfolio

Bayer A.G. (Berlin, Germany) announced on 6 June that it was to partner with Vancouver-based Acuitas to access their proprietary lipid nanoparticle technology as delivery vehicles for their gene therapy portfolio. Acuitas' cationic lipid nanoparticle technology has previously been clinically validated through its use in Alnylam Pharmaceuticals' Onpattro™, which has been approved for the treatment of transthyretin amyloidosis and a number of mRNA Covid-19 vaccine formulations.

Under the announced collaboration, Bayer and its gene therapy focused affiliate Asklepios BioPharmaceutical (AskBio) will gain access to Acuitas' lipid nanoparticle particle for the delivery of gene-editing RNA components to the liver.

Announcing the partnership Jost Reinhardt, Head of Cell and Gene Therapy, Pharmaceuticals Division, Bayer commented; “Developing therapies at scale is fundamental to provide breakthrough innovations to patients who have no time to wait. Adding Acuitas' clinically-validated and scalable LNP technology to our genomic medicine toolbox is another important step to advance our leadership in the field of cell and gene therapies” [11].

Croda announce new partnerships with Amyris & Botanical Solutions Inc

On 21 June, Croda International Plc (Snaith, UK) announced two new partnerships in Amyris Inc. (CA, USA) and Botanical Solutions Inc. (CA, USA) to enhance their supply chain for ingredients for vaccine adjuvants. Under the agreement with Amyris, the company will access a sustainable, biotechnology-derived, pharmaceutical-grade source for the adjuvant squalene. The agreement with Botanical Solutions will allow it access to a plant tissue cultured source for the QS-21 vaccine adjuvant.

Speaking at the announcement of these new partnerships Daniele Piergentili, President of Life Sciences at Croda, stated; “Our partnerships with Amyris and BSI are fully aligned with Croda's commitment to be the most sustainable supplier of innovative ingredients across our growth markets and with our pharmaceutical strategy to “empower biologics delivery”. Our ambition is to be able to offer vaccine developers the most appropriate adjuvant systems to maximize the efficacy of their antigen. These sustainably sourced technologies are a perfect extension to our broad spectrum of cGMP vaccine adjuvants, and we eagerly look forward to leveraging it globally across our customer base”.

Additionally, Croda also announced on June 5th that it had broken ground on a new lipid manufacturing facility at Lamar, Clinton County, Pennsylvania. The company claimed that this initiative was also in line with its ‘empower biologics delivery’ strategic focus and the 23,680 square-foot facility would enable it to manufacture ingredients for its lipid drug-delivery systems to be used for products including mRNA vaccines and gene editing therapies [12,13].

Nanoform & Celanese demonstrate enhanced drug delivery technology

In an announcement on 15 June, Nanoform Finland Plc (Helsinki, Finland) and Celanese Corp. (TX, USA), provided an update on their collaborative activities in the area of nanoparticle-enabled drug delivery. The companies discussed the combined application of Nanoform's CESS^® technology and the Celanese VitalDose^® EVA copolymer delivery technology to produce smaller implants capable of sustained drug release. The companies claim that the findings, which will be presented in July at the Biotech Outsourcing Strategies Conference in Basel, Switzerland, demonstrate the advantage of this combination approach in terms of drug-release profile.

Discussing the collaborative researcher Christian Jones, CCO of Nanoform stated; “We are delighted with these results and are excited about the continued opportunity to explore not only the technical benefits that the combination of these two technologies offer but, more importantly, the benefits that they bring to patients” [14,15].

Approvals & regulatory updates

VYVGART^® Hytrulo approved by the FDA as subcutaneous injectable for generalized myasthenia gravis

Halozyme Inc. (CA, USA) announced on 20 June that VYVGART^® Hytrulo, argenx's (Amsterdam, The Netherlands) a subcutaneous injectable containing efgartigimod alfa and hyaluronidase-qvfc has been approved by the FDA for generalized myasthenia gravis. VYVGART^® Hytrulo is formulated using Halozyme's ENHANZE^® proprietary drug-delivery technology.

ENHANZE^®, developed by Halozyme, is based on the recombinant human hyaluronidase PH20 enzyme, rHuPH20, which facilitates delivery of large volumes of formulation in the subcutaneous (SC) space via a mechanism that promotes local degradation hyaluronan allowing for an increased dispersion and absorption of co-administered therapeutics.

Announcing the approval Dr Helen Torley, President and Chief Executive Officer of Halozyme, stated; “We are pleased that argenx has received FDA approval for the subcutaneous form of efgartigimod, which reinforces their commitment to the patient community with a broadening of treatment options that brings flexibility for patients. We look forward to the multiple data readouts this year for subcutaneously administered efgartigimod in additional autoimmune conditions, with the potential to expand the number of approved indications and eligible patients” [16].

FDA approves Surmodics' SurVeil drug-coated balloon

It was announced on 20 June by Surmodics, Inc. (Eden Prairie, MN, USA) that the FDA had approved SurVeil™, a drug-coated balloon for use in percutaneous transluminal angioplasty. It had previously received CE Mark Certification in the EU in June 2020.

SurVeil™ is a proprietary device that includes a coating of drug-excipient on the balloon and is approved for the treatment of peripheral artery disease. It has been exclusively licensed to Abbott under a worldwide commercialization agreement. Under the terms of this agreement Surmodics manufacture and supply the product and benefit from a percentage of Abbott's product as well as a share of profits from Abbott's third-party sales. Additionally, Abbott will pay a $27 million milestone payment to Surmodics [17].

Clinical trials

Once-weekly insulin analog from Novo Nordisk meets phase IIIa clinical trial end points

It was announced on 24 June by Novo Nordisk (Bagsværd, Denmark) that the current phase IIIa clinical trials, named ONWARDS 1 and 3, have met their primary end points. These trials seek to evaluate the perform ance of Novo Nordisk's once-weekly insulin product, icodec. Data produced in the trials indicated that when compared with once-daily basal insulin, injections were reduced from seven to one per week. In addition, data also demonstrated that at 52 and 26 weeks, more insulin-naive Type 2 diabetic adults who were treated with once-weekly basal insulin icodec, achieved an HbA1c target of <7.0% without experiencing clinically significant or severe hypoglycemia when compared with once-daily basal insulin comparators.

Discussing the clinical trial data and the possible impact of this novel therapeutic Dr Julio Rosenstock, Lead Trial Investigator and Director of Velocity Clinical Research at Medical City Dallas and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, USA commented; “Time in Range provides additional information to help us assess glycaemic control and is an increasingly important tool to complement HbA1c measurements, which were substantially reduced by once-weekly basal insulin icodec. In ONWARDS 1, insulin icodec allowed people to spend significantly more Time in Range, with comparable Time below Range versus once-daily basal insulin glargine U100. A once-weekly basal insulin has the potential to change how we treat people with Type 2 diabetes needing basal insulin replacement” [18,19].

Sernova reports positive interim data for Cell Pouch™ system

Sernova Inc. (London, ON, Canada) announced positive interim data on June 26th for its phase I/II for its Cell Pouch™ system for the treatment of Type 1 diabetes. Sernova's proprietary implantable medical device the Cell Pouch™ system, which forms a “natural vascularized tissue environment in the body” to allow for the long-term survival and function of therapeutic cells for the treatment of chronic diseases. In this phase 1/2 clinical trial, following islet transplantation in the Cell Pouches, it was reported that patients in this cohort required only modest supplemental islet top-up via the portal vein for insulin independence, indicating successful islet grafts in the Cell Pouch.

Announcing the interim data presented Dr Philip Toleikis, president and CEO of Sernova commented; “We are very pleased to see these positive data for our T1D trial with Cell Pouch, and especially our 10-channel Cell Pouch configuration, as we pursue a ‘functional cure’ for patients with T1D. These additional data continue to confirm our understanding and provide verification of our estimates of islet dose thresholds and density required for optimal efficacy in this patient population”. “We continue to follow through on our commitment to rapidly enroll the study's second cohort, while setting the stage for Cell Pouch in combination with Evotec's iPSC derived islet-like clusters in our upcoming clinical trial” [20,21].

Pulmatrix presents PUR100 phase I data

Pulmatrix, Inc. (MA, USA), announced on 15 June that it was present phase I data at the American Headache Society 65th Annual Meeting (15–18 June) for its early-stage development product, PUR3100, an orally inhaled formulation of dihydroergotamine for the treatment of acute migraine. This formulation employs Pulmatrix's proprietary dry powder technology, iSPERSE™. iSPERSE has been developed to allow for the formulation of a range of therapeutics as small, dense, and dispersible particles which allows for highly efficient drug delivery and deep penetration of actives into the lungs, thus avoiding first-pass and systemic side effects. The company are partnered with several pharmaceutical companies including Cipla (India) and Nocion Therapeutics (MA, USA) to formulate a number of therapeutics using the iSPERSE.

Discussing the phase I results Dr Margaret Wasilewski, Chief Medical Officer of Pulmatrix, commented, “Based on these data showing rapid systemic exposure in the therapeutic range and the improved side effect profile compared with IV dosing, we believe that PUR3100 has the potential to meet the significant unmet needs of the approximately 40 million patients in the USA with acute episodic migraine. Based on these Phase I results, we are eager to advance PUR3100 into phase II testing and plan to file an Investigational New Drug Application (IND) with the US FDA in mid-2023. The phase II study would assess the safety and effectiveness of two dose levels of PUR3100. Pulmatrix is exploring partnership opportunities as a potential path forward for the Ph2 study” [22].

Alcyone receives an IDE for pivotal trial for its ThecaFlex DRx System

It was announced on 27 June by Alcyone Therapeutics Inc. (MA, USA) that the FDA has approved an Investigational Device Exemption (IDE) which will permit Alcyone to commence a pivotal trial of their implantable ThecaFlex DRx System. This pivotal study, named PIERRE, aims to evaluate both the safety and performance of Alcyone's proprietary subcutaneous port and intrathecal catheter system, ThecaFlex DRx, which will allow for repeated intrathecal access, cerebrospinal fluid aspiration and additionally the delivery of SPINRAZA^® to spinal muscular atrophy (SMA) patients. ThecaFlex DRx has received a CE Mark in Europe and Breakthrough Device Designation from the FDA.

It is anticipated that this pivotal trial will enroll up to 90 patients in total. The first stage of the trial will take place in a limited number of sites in the USA in mid-2023 and the second stage aims to have an enrolment of an additional 80 patients across the USA and Europe and will begin in 2024.

Announcing the FDA approval for the IDE, PJ Anand, Chief Executive Officer of Alcyone, commented; “Alcyone is excited to begin the process of evaluating the safety and performance of ThecaFlex in SMA patients being treated with SPINRAZA. ThecaFlex represents the culmination of a deliberate effort to design a delivery system specifically for repeat bolus intrathecal drug delivery. IDE approval and the impending start of the pivotal study are critical steps toward helping patients in need with a potential therapeutic delivery alternative and improved treatment experience” [23].

Early stage development

Bioengineered particles expand myelin-specific regulatory T cells & reverse auto-reactivity in murine multiple sclerosis model

It was reported in the Journal Science Advances on 2 June that research scientists at Johns Hopkins University (MD, USA) have demonstrated that biodegradable microparticles loaded with rapamycin and functionalized with a biased IL-2 fusion protein and a major histocompatibility complex class II loaded with a myelin peptide, which they have termed tolerogenic microparticles (Tol-MP) have been evaluated in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis. These early-stage studies have indicated that the novel microparticles facilitated sustained disease reversal in 100% of mice and full recovery in a reported 38% of the mice with symptomatic experimental autoimmune encephalomyelitis. The authors have indicated that this shows the Tol-MPs may have potential value in the treatment of autoimmune diseases.

The microparticles are manufactured with a combination of poly (lactic co-glycolic acid) (PLGA) and poly (beta-amino ester) (PBAE) as the authors claim this blend allows for increased conjugation of more protein than PLGA alone, leading to enhanced T-cell engagement [24].

Biora Therapeutics announces new patents for its NaviCap™ targeted oral delivery platform

Biora Therapeutics Inc. announced on 28 June the awarding of a family of US and European patents relating to its NaviCap targeted oral delivery platform. NaviCap is an ingestible device that has been designed for the targeted delivery of therapeutics focusing on the treatment of irritable bowel disease. Once ingested the device, a proprietary auto-location technology, GItrac™, identifies locations in the gastrointestinal tract, and a targeted release of therapeutics is then facilitated. Biora's lead program is for BT-600 a medical device/therapeutic for colonic delivery of a liquid formulation of tofacitinib, for the treatment of ulcerative colitis. Biora intends to submit an Investigational New Drug (IND) application to begin a phase I study in Q2 2023.

The recently issued patents are:

• EP3554539B1: “Treatment of a disease of the gastrointestinal tract with an integrin inhibitor”, EP3554485B1: “Treatment of a disease of the gastrointestinal tract with a JAK inhibitor and devices”, EP3601531B1: “Treatment of a disease of the gastrointestinal tract with live biotherapeutics”, EP3600416B1: “Treatment of a disease of the gastrointestinal tract with an immune modulatory agent released using an ingestible device”, EP3554541B1 entitled “Treatment of a disease of the gastrointestinal tract with a chemokine/chemokine receptor inhibitor”.

• US Patent No. 11,597,762: “Treatment of a disease of the gastrointestinal tract with an IL-12/IL-23 inhibitor released using an ingestible device”

• US Patent No. 11,426,566: “Treatment of a disease of the gastrointestinal tract with a TLR modulator”

• US Patent No. 11,523,772: “Treatment of a disease of the gastrointestinal tract with an immunosuppressant”

• US Patent No. 11,596,670: “Treatment of a disease of the gastrointestinal tract with IL-10 or an IL-10 agonist”.

Additionally, the European Patent Office has given notice that it intends to grant European Publication No. EP3554540A1 entitled “Treatment of a disease of the GI tract with an IL-12/IL-23 inhibitor released using an ingestible device” [25].

Cognigenics' intranasal CRISPR delivery bypasses the blood–brain barrier

It was announced by Cognigenics' (Boise, ID, USA) CEO John L Mee on 9 June that an animal study demonstrating intranasal delivery of neuromodulating gene therapies to the brain was published in PNAS Nexus. Discussing these early-stage preclinical study findings Director of Preclinical Studies Troy Rohn commented; “Our patent-pending CRISPR/Cas9 delivery system enabled us to bypass the blood brain barrier by intranasally administering therapeutics to reach the central nervous system via the neural pathways in the nasal cavity. In the study, a single dose significantly reduced anxiety in mice, demonstrating that complex behavioral traits can be directly modified by this non-invasive technique”.

Discussing the possible therapeutic benefit that this preclinical work demonstrates, Chief Medical Officer Barry J Linder, MD stated; “While our findings are preliminary, they may lead to a new class of long-lasting therapeutics with fewer side effects than SSRIs for mental health conditions including anxiety, depression and ADHD, as well as for some genetic conditions” [26,27].

CraniUS demonstrate preclinical convection-enhanced delivery cross the blood–brain barrier

CraniUS LLC (MD, USA) announced on 27 June the results of their pre-clinical study investigating their NeuroPASS device that offers the possibility of convection-enhanced delivery across the blood–brain barrier. In this study, gadolinium was delivered through catheters with CraniUS’ NeuroPASS device that was implanted in the skull space. According to the company, the NeuroPASS device can potentially provide a lower dose alternative to systemic drug delivery for indications that require delivery to the brain. CraniUS has indicated that these results will allow them to progress toward an FDA pre-clinical study with the intention of seeking an IND approval for a first-in-human study by the end of 2024 [28].

New nanoparticle could improve the delivery of mRNA-based vaccines

It was reported on 22 June from the Proceedings of the National Academy of Sciences (PNAS), Applied Biological Sciences that a Johns Hopkins University (MD, USA) research group has designed novel nanoparticles capable of mRNA delivery. The paper discusses pre-clinical data that indicates robust anti-tumor immune responses in several murine tumor models were achieved via targeted delivery to splenic dendritic cells. The nanoparticles are formed in a one-step, self-assembly process and the polymers used to form the nanoparticulate carriers are lipophilic poly(beta-amino esters). The authors claim the synthetic process to form the nanoparticles is agnostic to the mRNA encapsulated and therefore may represent a wide range of therapeutic options in the mRNA vaccine space [29,30].

Summary

June 2023 saw notable advances in the treatment of diabetes with positive phase 1/2 data for Sernova's proprietary implantable Cell Pouch™ system, Novo Nordisk's announcements of positive phase 3(a) data for its once-weekly basal insulin candidate, icodec, and their acquisition of a majority stake in BIOCORP facilitating access to Mallya, a Bluetooth-enabled device for pen injectors, for use in conjunction with their FlexTouch pen. Also, of note this month were announcements of therapeutic delivery options for novel biotherapeutics including a collaboration between Bayer and Aquitas for the delivery of gene therapy products, the establishment of a UK Intracellular Drug Delivery Centre for RNA delivery, and preclinical data from Cognigenics indicating that their intranasal CRISPR delivery platform can bypass the blood–brain barrier.

Financial & competing interests disclosure

The authors have 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.