Industry update, December 2022.

Abstract

Therapeutic DeliveryAhead of Print Industry NewsFree AccessIndustry update, December 2022Elaine HarrisElaine Harris *Author for correspondence: E-mail Address: Elaine.Harris@TuDublin.iehttps://orcid.org/0000-0003-1538-9947School of Chemical & Pharmaceutical Science, Technological University Dublin, IrelandSearch for more papers by this authorPublished Online:11 Apr 2023https://doi.org/10.4155/tde-2023-0016AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit Keywords: biodegradable polymerblood–brain barriercontrolled releaseextended releaselipid delivery systemmachine learningocular deliverytransdermalCompany NewsOramed provides clinical & commercial updates in a letter to shareholdersIn a letter to shareholders on 21 December 2022, Oramed (NY, USA) provided clinical and commercial updates including an announcement that top-line data for the phase III Oral Insulin Trial (ORA-D-013-1) is expected to be published in January 2023. This trial involved enrolment of over 700 participants for the treatment of Type 2 diabetes employing Oramed’s oral insulin candidate, ORMD-0801.Additionally, the company has indicated that its phase II NASH Trial had achieved its primary end point of safety and tolerability. The primary end-points for the trial with ORMD-0801 was in the treatment of nonalcoholic steatohepatitis (NASH) – a condition with no currently approved treatment options. The trial was conducted with 32 patients.The company also updates on early-stage development products including phase I trial for an oral COVID-19 vaccine trial and ORMD-0901, an oral glucagon-like peptide-1 (GLP-1) analog capsule for the treatment of diabetes.Oramed also disclosed a deal with the South Korean company, Medicox Co., Ltd. For distribution rights ORMD-0801 in South Korea. Commercial details for the deal include development milestone payments of up to $18 million and up to 15% royalties on sales [1].Vaxxas raises $23 million for needle free drug-delivery technologyVaxxas, the Brisbane-based company, developing a platform delivery technology initially developed in the University of Queensland (Brisbane, Australia) announced on 5 December 2022 that it had raised US$2 million to facilitate its clinical program including the development of its needle-free COVID-19 vaccine candidate. The delivery of the vaccine candidate relies on Vaxxas’ proprietary HD-MAP technology platform. HD-MAP is a process that readily employs injection molding to produce small, transdermal patches each containing thousands of very short (∼0.25 mm) microprojections for the delivery of therapeutics. These microprojections are designed to deliver therapeutics to immune cells directly beneath the surface of the skin while simultaneously triggering natural immunocellular alarms that facilitate rapid transport of the vaccines to lymph nodes thus eliciting a robust immune response.Announcing the achievement of a round of funding, Dr Paul Kelly, Founding Partner and Head of Healthcare at OneVentures, one of the lead investors said: “We believe Vaxxas’ needle-free vaccination technology will dramatically improve the availability, efficacy and safety of vaccines for a range of serious and prevalent diseases, including COVID-19 and influenza. We are pleased to continue supporting the Vaxxas team through this pivotal time in the company’s growth – as it applies a breakthrough approach to address some of the most significant unmet global needs in infectious and potentially other diseases” [2,3].Eli Lilly discontinues Ypsomed collaboration to pursue its own US insulin pump offeringIt was announced on 9 December 2022 by Ypsomed (Bergdorf, Switzerland) that Eli Lilly had decided to pursue the development of its own insulin pump project and therefore discontinue its relationship with Ypsomed in this area. The companies had entered a joint co-development agreement in November 2020 with a view to launching Ypsomed’s YpsoPump under Lilly’s brand in the USA. In announcing this decision, Ypsomed claims that it still plans to submit its YpsoPump system to the US FDA in the second half of 2023, and it now aims to commercialize the system with a new partner. The proprietary YpsoPump features a prefilled cartridge and adaptive automated insulin delivery system, combined with an interactive mylife CamAPS FX app [4,5].A $5 million gift to be used to advance trials for rare neurodevelopmental disordersMiami, Florida-based Foundation for Angelman Syndrome Therapeutics (FAST) announced on 2 December 2022 that it had received a $5 million gift to establish a clinic focus on translational research in rare neurodevelopmental disorders including the development of appropriate therapeutic delivery options for the treatment of Angleman Syndrome.Speaking at the announcement, Dr Allyson Berent, chief science officer at FAST said “This is the dawn of a new era. Today there are over 25 therapeutic programs in the development pipeline for Angelman syndrome, with a majority robustly funded by FAST. We are at a turning point, where we are ready for many of these programs to reach human patients for early stage first-in-human clinical trials, but most hospital centers do not have the bandwidth to keep up with this exploding need” [6].Collaborations & agreementsEvonik & Allay Therapeutics to collaborate to develop pain therapy implantsEvonik, the speciality chemical company based in Essen, Germany announced on 13 December 2022 that it had invested in the San Jose, Californian biopharmaceutical company, Allay Therapeutics. Under the terms of the agreement biodegradable polymers developed by Evonik will be employed in a novel implantable device for treating pain after knee surgery. The ability to provide controlled release of pain medication is seen as key to promoting the recovery process and reducing or even potentially eliminating the need for administration of opioid painkillers post surgery.Announcing the collaboration Bernhard Mohr, head of Evonik Venture Capital said “Allay’s pain products can become a game changer in postoperative pain management. They may reduce the problems that opioids bring, such as dependence, further hospitalization, lengthy rehabilitation and overall costs to the healthcare system” [7].Bioasis technologies announces merger with Midatech PharmaIt was announced on 13 December 2022 that Bioasis Technologies Inc. (CT, USA) is to merge with Midatech Pharma plc, based in Cardiff, Wales. Bioasis Technologies is a biopharmaceutical company focusing on leveraging its proprietary xB3™ platform to transport therapeutics based on epidermal growth factors across the blood–brain barrier. Midatech will bring its proprietary Midatech’s Q-Sphera technology to the newly merged company. This technology allows for the development of long-acting injectables by employing a 3D printing technology to create drug-loaded bioresorbable polymer microspheres. According to the terms of the agreement disclosed, Midatech will acquire from Bioasis shareholders 100% of all issued and outstanding common shares in the capital of Bioasis. Additional equity terms for the deal were also disclosed, which was due to close on 15 December 2022.The newly merged company will be called Biodexa Pharmaceuticals PLC and according to Mr. Stephen Stamp, incoming CEO of Biodexa; “By combining the two groups to create Biodexa Pharmaceuticals, we have the opportunity to reposition the enlarged group as an emerging biotech company focused on the development of therapeutics for rare diseases, supported by Midatech and Bioasis’s enabling drug delivery platforms. We continue to believe there is substantial value to be unlocked from Midatech’s MTX110, particularly in glioblastoma and to leverage our Q-Sphera technology. In combination with Bioasis’s promising development pipeline we have the opportunity to create a much stronger group” [8,9].Approvals & regulatory updatesFDA accepts Braeburn’s NDA resubmission for BRIXADI™Braeburn, a Pennsylvanian company that focuses on developing treatment options to tackle opioid use disorder, announced on 8 December 2022 that the FDA had accepted its New Drug Application (NDA) for BRIXADI (buprenorphine) has been accepted. BRIXADI extended release is intended as a weekly and monthly subcutaneous injections for the treatment of moderate to severe opioid use disorder. It uses a proprietary delivery system, FluidCrystal®* Injection Depot Technology, based on a lipid-based system that encapsulates a soluble active ingredient and forms a liquid crystalline gel upon subcutaneous injection facilitating controlled release of the active over an extended period of time.It is anticipated that, if approved, BRIXADI would be made available through a Risk Evaluation and Mitigation Strategy program and administration would take place in a registered healthcare setting. In announcing the acceptance of the NDA resubmission Braeburn confirmed that the anticipated Prescription Drug User Fee Act (PDUFA) action date is set for 23 May 2023 [10].EOFlow submits 510(k) application for its wearable insulin pumpIt was announced on 27 December 2022 that as part of its global expansion plan, Korean company, EOFlow had submitted a 510(k) application to the FDA for its wearable disposable insulin pump, EOPatch. The EOPatch is the 3rd generation version of EOFlow’s technology and is a 7 day wearable pump with a 3 ml reservoir employing a proprietary ultra-low-power, high-performance pumping technology.The company officially launched EOPatch in Europe in September 2022 and have also obtained approval from Indonesia in October 2022. Although the FDA approval and launch timeline are unclear; EOFlow plans to secure a US distribution partner in early 2023. Although the initial focus of EOFlow’s EOPatch is the treatment of diabetes the company is progressing with R&D for non insulin drugs with the wearable drug delivery system [11].Eyenovia unveils digital ocular drug delivery deviceEyenovia, Inc. (NY, USA) announced on 13 December 2022 acceptance by the FDA of its NDA for its ophthalmic spray product MydCombi™. This drug–device combination product has been designed to deliver therapeutics optically via its proprietary Optejet® drug-delivery technology platform. MydCombi delivers a first-in-class combination of tropicamide and phenylephrine. Confirming the acceptance of the resubmitted NDA the company indicated that the expected PDUFA date will be 8 May 2023.The Optejet drug-delivery technology platform allows for microdose formulations for ocular therapeutics employing high precision piezo-print technology. This technology addresses the typical overdosing encountered using conventional eyedroppers and facilitates the dispensing of a drug solution to the ocular surface in approximately 80 milliseconds which is designed specifically to overcome the ocular blink reflex.Announcing the acceptance of the NDA Michael Rowe, Chief Executive Officer of Eyenovia said “Acknowledgement of our MydCombi NDA is a significant step forward in our quest to bring a paradigm change in the way that topical eye drugs are developed and delivered, and we look forward to working with FDA during its review. If approved, MydCombi would be the first commercial product to leverage our proprietary Optejet drug delivery device, which we believe could bode well not only for our other internal development programs for presbyopia and progressive myopia but our ongoing partnering discussions as well” [12,13].TransCode therapeutics to proceed with first-in human clinical trialsTransCode Therapeutics Inc. (MA, USA) announced on 29 December 2022 that it had received authorization from the FDA to proceed with its first-in-human (FIH) Phase 0 clinical trial. This clinical trial will evaluate TransCode’s lead therapeutic candidate, TTX-MC138, in up to 12 cancer patients with advanced solid tumors. TTX-MC138 relies on TranCode’s proprietary iron oxide nanoparticle-based therapeutic RNA delivery system that maximizes targeted tumor uptake while minimizing clearance.Discussing the proposed trial TransCode’s Chief Executive Officer and co-founder, Michael Dudley said; “We are hopeful that this trial will demonstrate successful delivery of our lead therapeutic candidate to metastatic lesions in patients with advanced solid tumors. The delivery of RNA therapeutics to sites other than the liver has remained a significant challenge for decades. Overcoming this challenge would represent an unprecedented step in unlocking therapeutic access to a variety of well-documented genetic targets involved in a range of cancers and beyond” [14].RedHill’s Aemcolo® granted 5 year exclusivity extensionRedHill Biopharma Ltd (Tel Aviv, Israel and Raleigh, NC, USA) announced on 5 December 2022 that the FDA’s Exclusivity Board has granted 5 years’ exclusivity to Aemcolo, an orally-administered, delayed release, broad spectrum non systemic antibiotic approved for the treatment of travelers’ diarrhea caused by non invasive strains of E. coli in adults. This exclusivity is granted under the Generating Antibiotic Incentives Now (GAIN) Act Qualified Infectious Disease Product (QIDP) designation.Aemcolo is the first antibiotic engineered with Cosmo Pharmaceuticals’ (Dublin, Ireland) Multi Matrix Technology. Multi Matrix Technology is a proprietary platform technology designed to deliver the active pharmaceutical to the lower intestine. Due to its non systemic delivery using this delivery technology, Aemcolo has fewer side effects and a lower potential for interactions with other medications.In addition to being indicated for the treatment of traveller's diarrhoea, a proof-of-concept dose ranging trial is also being conducted with a new formulation in irritable bowel disease in Europe and other indications are currently pursued in minimal hepatic encephalopathy, acute uncomplicated diverticulitis and Small Intestine Bacterial Overgrowth [15].Clinical trialsUroGen releases data from the Phase III OPTIMA II studyData released on 2 December 2022 by San Francisco-based company UroGen indicates a median duration of response of 24.4 months for their candidate UGN-102 in a study looking at low-grade, intermediate risk non muscle invasive bladder cancer (LG-IR-NMIBC). The interim OPTIMA II study data was for 15 of the 25 patients enrolled and showed 65 percent complete response at 3 months. It was reported treatment with UGN-102 was generally well tolerated. UGN-102 employs a proprietary UroGen’s proprietary reverse-thermal RTGel™ technology to provide an extended release delivery profile.Announcing this data Mark Schoenberg, M.D., Chief Medical Officer, UroGen stated “UGN-102 uses a similar combination with a simpler delivery method to our currently approved chemoablative medicine and has shown a similar durability of response in LG-IR-NMIBC. If approved, UGN-102 would be the only primary non surgical treatment option for patients with LG-IR-NMIBC who often recur within 1 year of receiving surgery and continue to need repetitive surgeries for the rest of their life” [16].Melt pharmaceuticals report Phase II clinical trial results for sublingual tablet formulationOn 22 December 2022, Melt Pharmaceuticals Inc. (TN, USA) reported positive Phase II clinical data for their pivotal efficacy and safety study with MELT-300, a sublingual formulation containing midazolam (3 mg) and ketamine (50 mg), for procedural sedation during cataract surgery. The formulation has been designed to rapidly dissolve providing rapid onset of sedation and employs Catalent Inc.’s (NJ, USA) proprietary Zydis® delivery technology. The trial was carried out with over 300 subjects across nine states.Discussing the findings of the trial Larry Dillaha, MD, CEO of Melt Pharmaceuticals said “The clear, critical and positive findings for our procedural sedation primary end point allow us to confidently proceed with the development of this non-iv. option for cataract surgery. We believe the commercial appeal for offering patients and physicians the ability to achieve adequate sedation without the need to start an IV is an extremely attractive option for the nearly 5 million cataract surgeries performed every year in the US and the more than 20 million cataract surgeries performed around the world each year” [17].Arbutus completes Phase IIa enrolment in hepatitis B virus trialOn 13 December 2022 Arbutus Biopharma Corporation (PA, USA) announced preliminary data from the lead-in portion of its phase IIa clinical trial. This trial is to study the combination of its lead candidate, AB-729, with nucleoside analogue therapy and peginterferon alfa-2a for the treatment of patients with chronic hepatitis B virus Infection.Commenting on the initial data released Gaston Picchio, Ph.D., Chief Development Officer at Arbutus, said, “These preliminary phase IIa data are reassuring since they confirm previous phase Ib results showing that AB-729 is capable of consistently reducing HBsAg (hepatitis B surface antigen) while maintaining a safe and well-tolerated profile. We look forward to seeing the effects of different courses of IFN in combination with AB-729 to reduce HBsAg throughout 2023.”AB-729 is an RNA interference therapeutic which has been specifically designed to reduce all hepatitis B viral proteins and antigens including HBsAG and itAB-729 employs Arbutus’ proprietary, covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology which allows for subcutaneous delivery [18].Janssen presents data from their Phase Ib multiple myeloma studyJanssen Pharmaceuticals (Beerse, Belgium) presented data from their recent phase II multiple myeloma study (MajesTEC-2) at the 2022 American Society of Hematology Annual Meeting. Reporting these results on 10 December 2022 Janssen said the results Ib study of the triple combination of TECVAYLI™ (teclistamab-cqyv) in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and lenalidomide indicated a ‘manageable safety profile with no unexpected safety signals observed’. DARZALEX FASPRO DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase, Halozyme’s (CA, USA) proprietary ENHANZE® drug-delivery technology. ENHANZE enables the route of administration of some therapeutics to be modified and can facilitate subcutaneous rather than intravenous delivery options.The overall primary aim of the MajesTEC-2 study is to evaluate the potential immunomodulatory effects of daratumumab and lenalidomide to see if they could enhance the function of TECVAYLI, resulting in improved antimyeloma activity in a wider patient cohort [19].Early-stage developmentNovel microparticulate hydrogel drug delivery system reportedA novel microparticulate hydrogel drug-delivery system was reported in Nature: Scientific Reports by Hadidi and Pazuki published on 22 December 2022. The paper discusses the use of novel hydrogel microparticulates for the delivery of glatiramer acetate, which is used in the treatment of relapsing remitting multiple sclerosis. According to the paper’s authors, current treatment options are limited with a daily injection required. The authors report a formulation of chitosan-PLGA (poly (lactic-co-glycolic acid)) hydrogel-microparticles loaded with, prepared using a double emulsion method. In vitro drug release was studied for a period of 30 days. The in vivo efficacy of loaded microparticles was evaluated using established animal model for relapsing remitting multiple sclerosis. Results reported diffusion controlled sustained release of the active was achieved and the authors claim this could offer some benefits over current formulation options [20].NIH funds Illinois Tech project using machine learning to fully automate insulin deliveryIt was reported on 9 December 2022 that researchers at the Illinois Institute of Technology were to receive $1.2 million from the NIH to develop a machine learning system to allow an artificial pancreas to deliver insulin. The Principal Investigator for the project is to be Ali Cinar and the funding will allow 4 years of research to develop the machine learning system. The research aims to integrate the learning into Cinar’s artificial pancreas system with a focus on enhancing accuracy in insulin delivery. The project aims to analyze past behaviors through machine learning which can then be used to improve the device’s decision making algorithm. As the report says: ‘The advantage of powerful machine learning tools is to be able to tease out the secondary relations that exist. No matter how erratic people claim that their behavior is, there are always certain patterns that can be captured. It could be five patterns for someone who is very routine-based and 15 patterns for someone less routine-based. The system can look at how the day is developing on and then look at the dictionary of patterns to say, ‘Oh, this is similar to pattern no. 17, so let us assume that the rest of the day will go accordingly’ [21].SummaryDecember 2022 saw a number of positive clinical trial announcements for a wide range of therapeutic indications including multiple myeloma, hepatitis B and invasive bladder cancer. FDA notification of PDUFA action dates were obtained by Braeburn for its subcutaneous buprenorphine and Eyenovia's ophthalmic spray product MydCombi. In company news Vaxxas has announced it has raised $23 million to develop a needleless delivery technology, Evonik and Allay Therapeutics are set to collaborate to develop pain therapy implants and Eli Lilly discontinues Ypsomed collaboration to pursue its own insulin pump product.Financial & competing interests disclosureThe 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.