An Industry Update: the Latest Developments in Therapeutic Delivery Covering September 2018

Abstract

The present industry update covers the period 1–30 September 2018, with information sourced from company press releases, regulatory and patent agencies as well as scientific literature.

Various technologies using reformulations of know drugs with nanoparticles, hydrogels, aerosols, etc. emerged in new financing rounds (BioTime; CA, USA, SiSaf; Guildford, UK, Cassion Biotech; TX, USA), intellectual property protection (TFF Pharmaceuticals; TX, USA), repackaging (Leiters; CA, USA) and reformulation (Virpax Pharmaceuticals; PA, USA) demonstrating it does not have to be new active ingredients utilizing novel drug delivery formats. Innovative approaches such as magnetic particle loaded microorganisms (Polytechnique Montreal; Quebec, Canada) or new material combinations (University of Georgia; GA, USA) in the explorative field show that the permutation of materials, form factors and combinations with traditional and novel drug formats is sheer endless; and attracting attention of public granting agencies (SFC Fluidics; AR, USA and SBIR; DC, USA) as well as investors.

Keywords:

• aerosol
• blood–brain barrier
• diabetes
• nanoparticles
• repackaging
• transdermal

Business development

Financing

BioTime

On 4 September, BioTime (CA, USA) acquired $43.2 million through the sale of shares, which is the second round of sales following one earlier this year in January 2018. The company works on cell replacement, cell and drug delivery platforms, producing new tissues from pluripotent cells to replace impacted tissues and the HyStem^® hydrogel matrix formulation combined with cells, biologics or small molecules to deliver it to the treatment area. In this AgeX Therapeutics, Inc. (CA, USA) mediated share sale transaction with Juvenescence Limited (MA, USA), BioTime received $21.6 million to advance its clinical development pipeline [1].

SiSaf

SiSaf (Northern Ireland, UK) raised $3.5 million during September in a Series A capital raising with Vickers Venture Partners (Singapore, Singapore), Exen Capital (NY, USA) and Invest Northern Ireland (UK). The company has a porous nanosilicon-based drug delivery platform which creates a large surface area to enhance stability and bioavailability of difficult-to-formulate molecules. They are currently seeking drug development partners interested in developing controlled release and lower doses of their drug candidates. SiSaf intends to use the financing to continue its R&D efforts and expand into new markets [2].

Caisson Biotech

Caisson Biotech (TX, USA), funded and managed by Emergent Technologies (TX, USA), hired Pickwick Capital Partners (NY, USA) on 6 September to support commercialization of its drug-delivery platform HEPtune combined with its US and international patent portfolio to further its use in the industry. HEPtune – made of Heparosan, a natural sugar polymer and hence not immunogenic – substitutes for polyethylene glycol, a widely used drug delivery vehicle for a variety of drugs. This formulation has been proven to enhance proteolytic activity for coagulation Factor VII as opposed to unconjugated FVII or FVII conjugated with polyethylene glycol. Furthermore, HEPtune allows novel and extended patent protection for its drug conjugates and lowers manufacturing costs [3].

Licensing

Nemaura Medical

Nemaura Medical (Loughborough, UK) announced on 17 September they have executed a licensing agreement with an undisclosed pharmaceutical company pursuing a new transdermal patch product. Nemaura has developed a daily use transdermal patch for central nervous system indications which has completed clinical trials and regulatory US FDA submission. The company has multiple products in the pipeline, including complex injectables. In 2016, they received recognition from Frost & Sullivan (TX, USA) for their microneedle format in transdermal drug delivery and, in 2018, they received the UK Medilink National Award for Drug Delivery [4].

Consort Medical

Consort Medical (Hemel Hempstead, UK) made an agreement with AstraZeneca (Cambridge, UK) on 8 September for use of its metered-dose inhaler technology for the Bevespi Aerosphere treatment for patients with chronic obstructive pulmonary disease approved in April 2018. It will deliver its pressurized metered dose inhaler valves and actuators to AstraZeneca. The financial terms of the agreement were kept confidential [5].

Development & manufacturing agreements

Leiters

Leiters (CO, USA), a contract manufacturing company for eye diseases, announced on 19 September that it will provide FDA-compliant repackaging for Avastin. This new 2018 final guidance from the FDA concerns the combination, diluting and repackaging of biologics beyond its manufacturing license application. The company has initiated a considerable development process to meet these new, enhanced requirements for Avastin [6].

Ossianix

Ossianix, Inc. (PA, USA) announced on 4 September they were entering into a broader alliance comprising research and financial options with Novo Nordisk (Bagsværd, Denmark). The goal is to administer drugs to treat diabetes and other metabolic diseases through the blood–brain barrier. Ossianix's single domain VNAR antibodies will be combined with active ingredients produced by Novo Nordisk who will pursue the development and commercialization of the products. For its contribution, Ossianix will receive upfront, preclinical, clinical and commercial payments upon reaching milestones, financial support for R&D and royalties. Finally, Novo Nordisk can acquire all rights for each drug on already settled terms. Financial details of the agreement have not been disclosed [7].

AcuityBio

AcuityBio (MA, USA), who are currently developing new drug-delivery combination products and Cook Biotech, Inc. (IN, USA) who are working on advanced biomaterials and regenerative medicine, announced on 5 September they will be entering into a collaboration and co-development agreement. The agreement will involve AcuityBio's ABC103 lead candidate in preventing postsurgical lung cancer recurrence and Cook Biotech's patented extracellular matrix technology. ABC103 has a FDA orphan drug designation and combines surgical drug-eluting polymers with the cancer drug paclitaxel. Phase I clinical testing for ABC103 is intended for late 2019. Cook Biotech products are commercialized with several brand names, including Biodesign^® and OASIS^® and further uses for the ABC drug-delivery platform are currently being pursued. The terms of the agreements were not disclosed [8].

Kaléo

The pharmacy chain Walgreens (IL, USA) and kaléo (VA, USA), a privately held pharmaceutical company, agreed on 6 September to join together in order to improve access to kaléo's AUVI-Q^® epinephrine auto-injectors through Walgreens’ pharmacies. AUVI-Q is an FDA-approved prescription medication to treat emergency allergic reactions, such as anaphylaxis, with patients needing to seek immediate medical treatment afterward. Through the AUVI-Q AffordAbility program provided by kaléo, qualifying patients can acquire AUVI-Q at no cost. Some of its features are step-by-step user voice instructions and a second time-responsive auto-retractable needle system [9].

Regulatory news & approvals

Product approval

Teva

Bloomberg reported on 16 September, Teva Pharmaceutical Industries Ltd. (Haifa, Israel) and others are considering revisiting the use of deuterium for delivery of drugs. This heavier hydrogen isotope could slow the breakdown of compounds in the body, therefore allowing patients to take medications less frequently. The FDA is currently reviewing potential first medicines that could be made using deuterium. The drug is being tested by Teva to treat symptoms of Huntington's disease and additional data are expected to be submitted to the regulatory agency later in September 2018 and they aim to make it available to patients next year. Currently, there are no approved drugs to treat Huntington's beyond palliative treatment [10].

Clinical trials

SFC

SFC Fluidics, Inc. (AR, USA), a VIC Technology Venture Development™ company, announced on 20 September that it had received a $1.4 mill SBIR grant award to enable dual hormone patch pump development for Type 1 diabetes. Currently patients with Type 1 diabetes require multiple needle stick tests to measure blood glucose levels. SFC are hoping to develop a patch pump system with added safety and precise dose properties for automated insulin and glucagon delivery in order to achieve precise glycemic control by controlling delivery of insulin and glucagon at the same time. The patch pump is intended to be the same size as insulin-only patch pumps currently available. Furthermore, a sensor in the patch will deliver real-time flow confirmation on the correct dose administration alerting the user to any occlusions, leaks, depleted drug supply, accidental misloading or device failure [11].

Marius Pharmaceuticals

Marius Pharmaceuticals LCC (NC, USA) announced on 26 September promising data for their Phase III clinical trial for the evaluation of lead compound SOV-2012-F1 in male patients with hypogonadism. It is an oral testosterone replacement therapy and utilizes phytosterols to increase the lymphatic system absorption of it and favorable pharmacokinetics to improve the therapeutic window. Current standard of care is on injections or topical administration to return testosterone levels back to normal. The company's SOV-2012-F1 oral formulation of testosterone may help to address unmet needs enhancing absorption, enabling convenient oral dosing, hence increasing compliance [12].

Virpax Pharmaceuticals

On 12 September, Virpax Pharmaceuticals, Inc. (PA, USA) received FDA notification for its pre-investigational new drug application of DSF100 (1.3% diclofenac epolamine) – a topical inhaler to administer to an area of acute pain. DSF100 is developed in partnership with MedPharm, Ltd. (Guildford, UK). In the FDA response, Virpax got approval to pursue a new drug application enabling safety and efficacy human testing for the drug [13].

Patents

Mallinckrodt

The US Patent and Trademark Office has confirmed the validity of the claims related to five patents valid up until 2031 for Mallinckrodt's (MO, USA) Inomax (nitric oxide) gas delivery systems used for inhalation. Their patents were challenged by Praxair Distribution, Inc. (CT, USA). The FDA-approved Inomax system was designed to enhance oxygen delivery in neonatal patients suffering from hypoxic respiratory failure and pulmonary hypertension while supported with ventilators and medication [14].

TFF Pharmaceuticals

TFF Pharmaceuticals (TX, USA), is a start-up biopharmaceutical company committed to the development and marketing of novel inhaled drugs to treat chronic respiratory diseases. On 26 September, they had received a European Patent Office Notice of Intent to grant a patent application named “Formation of Stable Submicron Peptide or Protein Particles by Thin Film Freezing,” for oral, depot, pulmonary and transdermal drug delivery. The company is capable of producing dry powder inhaler versions of drugs, small molecules, biologics and combinations, using the active ingredient to address initially difficult to formulate compounds. The technology is licensed exclusively from the University of Texas Austin (USA) [15].

Publications

Polytechnique Montreal NanoRobotics Laboratory

Researchers at the Polytechnique Montreal NanoRobotics Laboratory (Montreal, Canada) investigated bacteria with magnetic capabilities as a means to deliver targeted loads of chemotherapeutic drugs to tumors. Existing nanocarriers typically reach tumor sites through the blood circulation but this passive delivery fails to penetrate the tumor sufficiently leaving malignant tissue, especially hypoxic tumor tissue, intact. The scientists have used the bacterium Magnetococcus marinus, which lives in deep, low oxygen waters and uses magnetic nanocrystals and oxygen sensors to navigate to deeper waters. In their experiments, Polytechnique Montreal NanoRobotics Laboratory has targeted a tumor using a magnetic field to deliver the drug and penetrate it deep into the hypoxic tumor areas. By attaching drug vesicles to the bacteria cells, 55% of the drug reached the tumor as compared with 2% when the drug was used alone [16].

University of Georgia

Gold nanoparticles have previously been successfully used in drug delivery despite the high cost associated with the starting material. Researchers at the University of Georgia (GA, USA) have now identified iron oxide particles with similar properties when combined with gold nanoparticles, resulting in a hybrid nanostructure with the combined properties of both materials. One of the characteristics of gold nanoparticles useful for drug delivery is that it is light and through conversion by heat it allows the release of a drug to target cells, for example cancer cells [17].

Oregon State University

As a feasible treatment of Niemann Pick Type C1, a rare genetic disorder that affects lysosomal storage and is ultimately fatal in over 50% of patients before the age of 10, researchers from Oregon State University (OR, USA) have investigated a nanotech drug delivery system. The current treatment uses an HP Beta CD drug that needs to be injected directly into the brain and can cause serious hearing loss and lung damage. High dosages are also required as only 0.2% of the drug crosses the blood–brain barrier. To overcome this, the scientists at Oregon State University utilized a nanotech drug delivery approach attaching the beta drug to a nanosized lipid that transfers the drug into brain cells five-times more effectively and, as a result, a much lower dose is required to be administered intravenously rather than directly into the brain [18,19].

Financial & competing interests disclosure

O Steinbach is an employee of Royal Philips Electronics North America Corporation. The author has no other 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 apart from those disclosed.

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