Industry update: the latest developments in the field of therapeutic delivery, August 2022.

Therapeutic DeliveryAhead of Print Industry NewsFree AccessIndustry update: the latest developments in the field of therapeutic delivery, August 2022Peter TimminsPeter Timmins *Author for correspondence: Tel.: +44 1484 473 102; E-mail Address: p.timmins@hud.ac.ukhttps://orcid.org/0000-0002-5840-0678Department of Pharmacy, University of Huddersfield, Queensgate, Huddersfield, HD1 3DH, UKSearch for more papers by this authorPublished Online:18 Jan 2023https://doi.org/10.4155/tde-2022-0053AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Business newsAcquisitions, mergers, licensingPfizer & Global Blood TherapeuticsSickle cell disease (SCD) is a group of genetic disorders arising from defects in the gene coding for haemoglobin. The sickle-like, misshapen red cells seen under a microscope in blood of sufferers is a hallmark of the disease, which is most prevalent in populations of African, Caribbean, Middle Eastern and South Asian descent. Symptoms of the disease include very painful sickle cell crisis episodes, increased susceptibility to serious infections and anaemia. Tiredness, lung problems, delayed growth and strokes can also occur. Currently, there are limited treatment options, including pain management with analgesics, antibiotics to manage infections, hydroxyurea to help with symptoms, and, if necessary, regular blood transfusions. A novel, oral therapy, vexelotor, Oxbryta®, from Global Blood Therapeutics (GBT, CA, USA), became available in 2019. Through direct activity on the polymerization of the faulty haemoglobin, which leads to red cell sickling, it offers an alternative with a clear action on disease mechanism. Now, Pfizer (NY, USA) and GBT have announced an agreement under which GBT will be acquired by Pfizer [1]. This gives Pfizer not just vexelotor, but a pipeline of potential SCD therapeutics, including GBT601 (GBT021601), a next-generation sickle haemoglobin polymerization inhibitor that is more potent than vexelotor and may offer more convenient dosing, and inclacumab. This antibody targets P-selectin and, dosed by infusion every 3 months, can reduce incidence of disease crises where sickled red cells can occlude capillaries and lead to pain. Inclacumab, previously under development by Roche (Basle, Switzerland) for coronary artery disease, is currently in phase III clinical trials, and GBT601 is currently in phase II of a phase II/III study. There are also several preclinical SCD assets [2]. The acquisition by global big pharma Pfizer offers the potential to accelerate the distribution and availability of these SCD treatments to parts of the world impacted the most by these diseases.Genentech & Kiniksa PharmaceuticalsKiniksa Pharmaceuticals (Hamilton, Bermuda) has announced a licensing deal with Genentech, a member of the Roche group (CA, USA) for its monoclonal antibody vixarelimab. Vixarelimab targets the oncostatin M receptor beta, which is involved in oncostatin M and IL-31 signaling. These two cytokines are implicated in pruritus, inflammation and fibrosis. While the transaction assigns global rights across all indications, Genentech will be focussed on fibrosis and the asset will be pursued in respiratory diseases. Kiniksa has stated that it will continue and complete its ongoing phase II clinical programme for vixarelimab in prurigo nodularis. The capital received will be invested by Kiniksa in expanding its cardiovascular franchise around its already approved medicine rilonacept (Arcalyst®) [3]. Rilonacept is the only therapy currently approved by the US FDA for the treatment of recurrent pericarditis, and it is also approved for the treatment of the rare diseases cryopyrin-associated periodic syndromes (CAPS), familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and deficiency of IL-1 receptor antagonist (DIRA) [4,5].Merck & StarpharmaA new research agreement has been signed between Starpharma (Melbourne, Australia) and Merck (NJ, USA), known as Merck Sharp and Dohme or MSD outside of the USA and Canada. This involves Starpharma's proprietary polylysine dendrimer technology (DEP®), wherein DEP dendrimer conjugates will be designed synthesized for testing and characterization by MSD. The agreement follows an earlier one between the two companies around DEP antibody–drug conjugates (ADCs) [6]. Dendrimer-based ADCs have the potential to increase drug payload per antibody molecule relative to non-dendrimer ADCs, with greater drug homogeneity, having specific and reproducible site of attachment on the antibody and with reduced potential for aggregation. In addition to MSD, Starpharma has dendrimer drug-delivery partnerships with AstraZeneca and Chase Sun Pharmaceutical [7].Alcon & Aerie PharmaceuticalsExtending its portfolio of approved, clinical, and preclinical product candidates, Alcon (Geneva, Switzerland), a leading global ophthalmic therapies company, has announced it will acquire Aerie Pharmaceuticals (NC, USA). The acquisition brings two commercial glaucoma therapy products netarsudil ophthalmic solution (Rhopressa®) and netarsudil with latanoprost ophthalmic solution (Rocklatan®), a phase III product candidate AR-15512 for dry eye disease and several other early clinical and preclinical potential products. Alcon has pursued multiple acquisitions in the last couple of years, including brimonidine with brinzolamide (Simbrinza®) for glaucoma acquired from Novartis (Basle, Switzerland) in 2021 and loteprednol etabonate (Eysuvis®) for dry eye disease and a higher strength loteprednol etabonate suspension (Inveltys®) for post-operative inflammation and pain management from Kala Pharmaceuticals (MA, USA) in 2022 [8]. The Aerie products have novel mechanisms of action, with netarsudil being a Rho kinase (ROCK) inhibitor that relaxes the trabecular meshwork thus affecting draining of the aqueous humour from the eye via the anterior chamber and lowering intraocular pressure. AR-15512 acts as an agonist on cold-sensitive thermoreceptors (TRPM8) located on the cornea and eyelids that play a central role in tear film homeostasis, causing an increase in tear fluid production [9].Amgen & ChemoCentryxAmgen (CA, USA) and ChemoCentryx (CA, USA) have announced that ChemoCentryx is to be acquired by Amgen in a deal valued at approximately $3.7 billion [10]. ChemoCentryx focusses on orally administered therapeutics for the therapy of autoimmune diseases, inflammatory disorders and cancer. The acquired portfolio includes a marketed product, avacopan (Tavneos®) along with three early-stage inflammatory disease drug candidates (one phase II-ready targeting inflammatory bowel disorders) and an orally dosed immuno-oncology checkpoint inhibitor. Avacopan is a complement 5a receptor (C5aR) antagonist and is a first-in-class treatment for severe active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis. By preventing the mobilization of potentially tissue damaging immune system cells it has a novel anti-inflammatory – not immunosuppressive – mechanism that can preserve the function of the immune system e.g., against infections. It was approved in the USA in late 2021 [11], and is also marketed in Europe [12], Japan and Canada. ANCA-associated vasculitis is a group of rare autoimmune diseases that are typified by inflammation of small blood vessels. This inflammation results from antibodies binding to proteins in neutrophil cytoplasm causing release of compounds from the neutrophil that damage blood vessel walls, and from neutrophil migration through the vessel wall, inducing inflammation in the surrounding tissues. These two processes promote recruitment of more neutrophils to the damaged vessels and tissues thus continuing and worsening the situation. It can go on to produce serious damage and dysfunction especially of the kidneys, but also of the lungs, and other organs, and there is risk of sepsis [10,13]. Standard therapy to date has been use of broadly acting immunosuppressive therapy along with corticosteroids, which carries a risk of infections which can become life threatening. The transaction is expected to complete toward the end of 2022.Gilead sciences & MiroBioIn a further deal in the inflammatory disease space this month, Gilead Sciences (CA, USA) and MiroBio have announced an agreement under which Gilead will acquire MiroBio (Oxford, UK). The UK-based biotech was spun out of Oxford university in 2019 and, applying its I-ReSToRE discovery engine, has been working on discovering agonist antibodies that target immune inhibitory receptors to restore immune balance. In this way, therapeutics discovered by the company may be able to selectively and precisely reduce the overactive immune system responses that underpin inflammatory diseases without being broadly immunosuppressive. Among the assets acquired in the deal are one phase I clinical stage asset, MB272 a selective agonist of immune inhibitory receptor B- and T-lymphocyte attenuator, and one advanced preclinical candidate MB151 which is a PD-agonist, interestingly thus working by the opposite activity to checkpoint inhibitors that are at the forefront of immuno-oncology therapy [14,15].PolyPid & Advanz PharmaPolyPid (Petach-Tikva, Israel) has announced the agreement of an exclusive licence for its doxycycline surgical site infection prevention technology with Advanz Pharma (London, UK). The doxycycline product, D-PLEX100, provides prolonged, controlled release of a localized high concentration of the antibiotic at the surgical site over 30 days to prevent surgical site infections following abdominal or cardiac surgery, and potentially deal with antibiotic-resistant infections. D-PLEX100, is currently under evaluation in a phase III trial [16]. The delivery system PLEX (Polymer-Lipid Encapsulation matriX) employed in the product is based on a polyester biodegradable matrix, polyglycolide (PGA), polylactide (PLA), polylactide-coglycolide (PLGA) or mixtures of these polymers combined with an amount of sterol or a phospholipid – typically phosphoethanolamine – sufficient to saturate the polymer matrix. This mixture, in a suitable solvent, is combined with a second solution containing the drug and phospholipid e.g., phosphatidylcholine, and the solvent is removed from the combined solutions to yield the drug-containing, lipid-saturated polymer drug-delivery system [17]. D-PLEX100 has received Breakthrough Therapy designation from the US FDA for the prevention of surgical site infections in patients undergoing colorectal surgery, as well as receiving three Qualified Infectious Disease Product designations and three Fast Track designations [16].Aptar Pharma & PharmaxisAn option on a high delivered dose dry powder inhaler, the Orbital® dry powder inhaler, agreed between Pharmaxis (Frenchs Forest, Australia) and Aptar Pharma (IL, USA) in 2021 has advanced to an exercise of that option. The exercise gives Aptar a worldwide license to the device, along with an opportunity to acquire the technology outright [18]. The Orbital inhaler allows for doses of up to 400 mg to be delivered without reloading the device. It was originally developed as a product improvement for the spray dried mannitol for inhalation product, Bronchitol®, marketed in many territories by Pharmaxis as a treatment for cystic fibrosis. The current market inhaled mannitol product requires patients to load an inhaler with a mannitol-containing capsule that on actuation of the device delivers 40 mg of mannitol. The spent capsule is removed, a new one is inserted, and the actuation repeated. The dosing in this way has to be undertaken ten-times to deliver the required 400 mg dose. With the Orbital inhaler, all capsules required for the total dose are together in the device and the patient just primes the device and inhales, repeating that simpler action until all the drug is administered. The Orbital device holds the capsule in a puck that on actuation undergoes an orbital motion to deagglomerate, disperse and aerosolize the powder being inhaled [19,20]. For drugs having doses in the high tens to mid hundreds of milligrams per dose that were previously difficult to bring to practice in a dry powder inhaler, the addition of Orbital to the portfolio of inhaled drug devices available through Aptar now offers potential to explore them.CollaborationsRoche & Poseida TherapeuticsCalifornia, USA-based Poseida Therapeutics has a range of genetic engineering technologies it can apply to the creation of novel cell and gene therapies, including non-viral DNA delivery (piggyBac®), site-specific gene editing (Cas-CLOVER™) and also gene delivery based on nanoparticles or adeno-associated virus (AAV) vectors. The company has announced a global collaboration with Roche, to advance existing and next generation allogenic CAR-T cell programmes for therapy of haematological cancers [21]. Allogenic CAR-T cells are essentially ‘off the shelf’, harvested from donors and processed for storage until required for use, as opposed to autologous CAR-T cells where cells are harvested from the patient for modification and prepared for infusion back into the patient. Hence the time from identifying the need for cell therapy to provision to the patient is shortened. Poseida is pursuing stem cell memory T-cells in its approach, which are less well differentiated than later stage T cells, such as effector T cells, and have advantages in clinical response and duration of response, toxicity, and effective bone marrow engraftment. Stem cell memory T-cells are long lived, self-renewing and multipotent, key attributes to enable an off the shelf product [22]. The collaboration covers a phase I clinical asset for the treatment of multiple myeloma, P-BCMA-ALLO1, plus P-CD19CD20-ALLO1, for B-cell malignancies that will enter initial clinical studies in 2023. The collaboration will also encompass research into improvements in allogenic CAR-T therapies to discover new product candidates.Merck & CerevanceMerck and Cerevance (MA, USA) have announced a strategic collaboration to apply Cerevance's Nuclear Enriched Transcript Sort sequencing (NETSseq) technology platform to identify novel targets for Alzheimer's disease. Cerevance will also be out-licensing one of its discovery stage programmes to Merck. The value of the NETSseq approach is proven, in that it enabled the discovery of a novel target for Parkinson's disease against which Cerevance developed a product, CVN424, which has returned favourable results in a phase II trial [23]. NETSseq uses antibodies and RNA probes to tag specific cell types in brain tissue to allow their sorting and eventually deliver a cell type-specific transcriptome. Identifying proteins from this that are either over- or under-expressed in diseased brains can then enable the development of agents against those targets [24]. As well as assets in clinical development for psychiatric disorders, Cerevance is also advancing preclinical assets for the therapy of Parkinson's disease and for neuroinflammation in Alzheimer's disease [25].Merck & Orna TherapeuticsA new investigational class of engineered circular RNA (oRNA) therapies are the subject of a collaboration between Orna Therapeutics (MA, USA) and Merck. The collaboration will span discovery, development and commercialization and cover vaccines as well as therapeutics in infectious diseases and oncology. Rights to an oRNA lipid nanoparticle platform (including technology from a joint venture with MA, USA-based RNA delivery company ReNAgade Therapeutics) will be retained by Orna, and the company will also retain and continue to develop other wholly owned programs is oncology and genetic diseases. The oRNAs are created from linear RNA and the circularized molecules show better in vivo stability than the linear counterparts. They can produce larger quantities of target therapeutic protein than their linear counterparts, can have an improved immunogenicity profile, and may be more effectively formulated into lipid nanoparticles for delivery [26].Mersana Therapeutics & GSKA co-development and commercialization collaboration has been agreed between GSK (London, UK) and Mersana Therapeutics (MA, USA) around the latter's XMT-2056. GSK has gained an option for this novel ADC that targets an epitope of HER2 and delivers a STING agonist to activate the innate immune system against the targeted tumour, via tumour resident immune cells and in tumour cells themselves. This is suggested as being beneficial over conventional untargeted STING stimulation approaches that only activate immune cells. Deploying ADCs to deliver immunotherapeutic agent in cancer therapy is distinct from conventional thinking with ADCs, where the antibody is used for its intrinsic therapeutic effect and to deliver and target cytotoxic agents to cancer cells. A phase I trial of XMT-2056 is planned to evaluate its potential in a range of HER2-expressing tumours including breast, non-small-cell lung and gastric cancer [27,28].Sosei Heptares & AbbVieSosei Heptares (Tokyo, Japan/Cambridge, UK) and AbbVie (IL, USA) have announced a new drug-discovery collaboration, extending their existing relationship. This new effort is directed toward identifying small molecule potential therapeutic agents that modulate novel G protein-coupled receptor (GPCR) targets associated with neurological diseases. Employing its proprietary GPCR-targeted STaR® technology and its structure-based drug design platform to identify drug candidates, Sosei Heptares, will undertake the activities up to the completion of work enabling submission of regulatory applications to initiate phase I trials. AbbVie can then exercise its option to license up to three programs at that stage, and then be responsible for subsequent clinical, regulatory, and commercial development work [29].Innovent Biologics & SanofiWith the potential to expand its presence in China, Sanofi (Paris, France) has announced a collaboration with Innovent Biologics (Suzhou, China/CA, USA) to accelerate the development and commercialization of the CEACAM5-targeted ADC tusanitamab ravtansine (SAR408701) and the extended half-life, PEGylated, recombinant human IL-2 variant SAR444245. This has preferential binding to the low affinity IL-2 receptor relative to the alpha chain of the high affinity receptor, due to the presence of the PEG chain. CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule 5) is a cell surface glycoprotein highly expressed in some cancers, including non-small-cell lung cancer (NSCLC) and gastric cancer. Tusanitamab ravtansine is currently in phase III trials in several countries, including China, as second line therapy for NSCLC and is in phase II trials as first-line therapy for NSCLC and gastric cancer. SAR444245 is in global phase II trials for the treatment of skin cancers, NSCLC/mesothelioma, head and neck cancer, gastrointestinal cancers, and lymphoma. Trials in China under the collaboration will include studies of the Sanofi compounds in combination with Innovent's PD-1 immuno-oncology inhibitor sintilimab (Tyvyt®) [30].Ipsen & Marengo TherapeuticsIpsen (Paris, France) and Marengo Therapeutics (MA, USA) have announced a partnership to develop two preclinical drug candidates discovered using Marengo's STAR (Selective T Cell Activation Repertoire) platform. Although not disclosed in the announcement, they may be STAR002 and STAR003, based on information on Marengo's website [31,32]. Bi-specific antibodies discovered using this platform are designed to target specific subsets of the Vβ protein of the T cell antigen receptor and at the same time bind to a co-stimulatory site on the same cell to very specifically and robustly activate and enable expansion of a selected T cell population. This has the potential for high selectivity, potent efficacy, good safety, and durable activity in providing novel immuno-oncology therapeutic agents. Through the collaboration, Marengo will focus on preclinical work to identify drug candidates and Ipsen will deploy its development and commercialization experience to take candidates forward through clinical studies and regulatory submission [33].GentiBio & Bristol Myers SquibbEffector T cells, which activate the immune and inflammatory response, and regulatory T cells (Tregs) that suppress the immune response to keep it at the necessary level, have their balance disrupted in autoimmune and inflammatory diseases. Insufficient numbers, or reduced activity of Tregs results in an inappropriate immune system response, manifesting as the symptoms of those diseases. GentiBio (MA, USA) has developed approaches to engineering more abundant T cell forms, transforming them into Treg phenotypes with enhanced properties, including stability, enhanced potency, and selective targeting to diseased tissues. GentiBio's Dura-Reg™ genetic engineering platform provides for that transformation of the broader population of T cells into Tregs, and further CAR and TCR editing provides for tissue targeting. Modifying IL-2 signaling in the engineered Tregs through low dose rapamycin enhances potency and durability of the cells. This overcomes the problems with harvesting Tregs from a patient for modification and reinfusion as they are a rare and heterogenous population with poor stability in vivo with risk of transformation into effector cells that would exacerbate the disease being treated [34,35]. Now the clinical potential of this technology is to be explored in a collaboration announced between GentiBio and Bristol Myers Squibb (NY, USA), under which GentiBio will research the cell engineering and scalable manufacturing processes for disease-specific Tregs against multiple targets and where Bristol Myers Squibb will take three of those programmes into clinical studies. Specifically, Bristol Myers Squibb will focus on treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn's disease, where current therapeutic approaches can involve use of systemic anti-inflammatory agents or non-specific immunosuppression, with risk of undesirable activity outside of the gastrointestinal system. The use of engineered Tregs may allow for a more targeted approach [36].Other business newsDelayed-release galantamine prodrug formulation exhibits favourable bioequivalence to established therapyGalantamine, an alkaloid originally isolated from the Eastern European snowdrop Galanthus woronowii, is a cholinesterase inhibitor and an allosteric modulator of the nicotinic acetylcholine receptor, thus having benefit in improving cholinergic activity in the central nervous system. It is used in the treatment of mild to moderate Alzheimer's disease. It has however challenges with tolerability, mostly gastrointestinal such as nausea, vomiting, gastrointestinal discomfort, and loss of appetite. Consequently, patients treated with galantamine start on a low dose that is gradually increased to a therapeutic effective dose to help manage those side effects, but this extends the time to reaching an effective dose and achieving symptom control. To improve the tolerability of galantamine and allow a more rapid attainment of treatment with an effective dose, Alpha Cognition (Vancouver, Canada) have developed a prodrug of galantamine, and formulated it as a delayed release dosage form (known as ALPHA-1062) to minimise concentrations of galantamine in the gut lumen. Drug is released only after the dosage form has left the stomach, and the conversion of the prodrug to the active drug occurs after absorption, avoiding free galantamine exerting pre-absorption cholinergic activity and causing the gastrointestinal side effects. One requirement to rapidly advance ALPHA-1062 to a regulatory filing was to demonstrate bioequivalence for galantamine dosed as the delayed release prodrug to a reference, already approved extended-release galantamine formulation. Alpha Cognition have just announced the successful conclusion of such a trial, with steady state bioequivalence being confirmed [37], adding to earlier findings of bioequivalence of a single dose of ALPHA-1062 to a single dose of an already approved immediate release galantamine product [38]. While head-to-head comparisons were not been conducted, the company has suggested incidence of gastrointestinal side effects in the bioequivalence studies were lower than those given in labelling for approved galantamine products [39]. Alpha Cognition is looking to a second quarter 2023 US regulatory filing for ALPHA-1062Vector BioPharma established by Versant Ventures to advance high-payload, tissue-specific gene-delivery platformHealthcare venture capital leader Versant Ventures (Basle, Switzerland) has announced the commitment of $30 million to the launch of Vector BioPharma (Basle, Switzerland) in support of advancing its engineered virus-like particle gene-delivery technology. This technology is based on a replication-deficient human adenovirus 5 (HAdV5) vector (viral genetic material-deficient), which is modified through the addition of a protein shield covering much of the capsid. This reduces clearance of the virion particles by the liver and inhibits immune system recognition. The virus-like particle surface is further modified by the incorporation of adapter proteins designed to target tumour-specific receptors such as EGFR and HER2. The use of HAdV5 allows for large, inserted genome packaging, up to 36 kb, such as DNA-encoded therapeutics, as opposed to the 4.7 kb deliverable via vectors such as AAV. The greater payload allows therefore for delivery of not only single genes but multiple genes in the same carrier. The engineered virus-like particle technology comes out of the University of Zurich, Switzerland [40,41].Latch medical intradermal delivery technology gains investment support from West Pharmaceutical ServicesWest Pharmaceutical Services (PA, USA), a provider of components and technologies to developers and manufacturers of parenterally administered drugs, has taken a minority ownership stake in the intradermal drug delivery device company Latch Medical (Dublin, Ireland). The latter company, spun out of University College Dublin, has created two microneedle array device technologies, Pharma Latch Coated and Pharma Latch Hollow. The Coated version is based on solid needles having a dry coating on the needles containing the therapeutic agent. On application of the device to the skin, the microneedles achieve near full length penetration, and they then dissolve in the moisture of the dermal environment to deliver their payload. The device is straightforward to use, having a novel ‘click on' mechanism to enable skin penetration of the interlocking microneedles and achieve self-retention of the device, without need for additional applicators. The 'click off” mechanism disengages the device from the skin surface to facilitate its removal. The Hollow variant has hollow microneedles, and a similar 'click on/click off' arrangement to the coated device allows placement on and attachment to the skin, with dermal penetration by the needles. This device has a Luer Lock/Slip port to provide for attachment of a syringe to enable use of the device to provide for intradermal dosing of a liquid formulation through the skin in a ‘needle-free’, virtually painless way. The investment will enable to start up to further advance the development of the two devices [42,43].ElevateBio & Boston Children's Hospital form company to develop allogenic immune cell therapy therapeuticsThe potential of allogeneic, ‘off the shelf’, immune therapies was noted earlier in this article in the discussion of the Roche/Poseida collaboration and a further announcement in this area has come from ElevateBio (MA, USA), disclosing the formation of a new company co-founded with Boston Children's Hospital and Dr George Daley of Harvard Medical School to develop allogenic immune therapies based on a novel platform. The platform is based on transforming induced pluripotent stem cells (iPSCs) into mature immune cells through a proprietary process, overcoming the tendency of iPSCs to become immature blood cell types. It additionally enables the creation of a range of immune cell subtypes that closely resemble the mature T cells that occur in adult blood. Daley's discovery of repressing the histone methyltransferase EZH1 during iPSC differentiation to yield the mature cells is key to the technology, the mature cells being referred to as EZ-T cells. On activation they give rise to long lived memory T cells, which contribute to lasting remission in using them to treat cancer. Cells with cytotoxic and cytokine-producing capabilities CAR engineered to target CD19 show in vitro activity against lymphoid tumour cells comparable to CAR-T cells engineered from adult blood and showed good efficacy in a mouse xenograft model of diffuse large B-cell lymphoma. The newly formed company is the first company to be created through an ongoing 5-year collaboration between ElevateBio and Boston Children's Hospital [44].Nasal delivery of nalmefene for opiate overdose advances toward regulatory review through BARDA grantOpiant Pharmaceuticals (CA, USA) has announced that it has been granted an additional approximately $2.1 million by the Biomedical Advanced Research and Development Authority (BARDA), an organization within the US Department of Health and Human Services that supports the development of diagnostics, vaccines, and treatments for public health medical emergencies, disease pandemics, antimicrobial resistance and emerging infectious diseases [45]. The new funding will support the preparation of Opiant's New Drug Application (NDA) for nasally delivered nalmefene (OPNT003) for the treatment of opioid overdose. There is an overdose crisis in the USA, driven by the availability of illicit synthetic opioids, with over 70,000 deaths linked