15 Feb Emerging Paradigms in the Anticoagulant Industry
Anticoagulants have wide applications for prevention of blood clots in treatment of conditions such as pulmonary embolism, deep vein thrombosis (DVT), atrial fibrillation, stroke management and thromboembolic disorders. According to estimates available on CDC, approximately 900,000 people are affected by DVT/PE each year in the U.S and 60,000-100,000 succumb to it.
These numbers are likely to rise in the future owing to an ageing population and increasing risk of stroke due to lifestyle changes, improper diet, etc. Warfarin, a vitamin K antagonist (VKA), is the most common Oral anticoagulant, which has limitations in its use and management such as intracerebral bleeding, toxicity etc. A new generation of oral coagulants have been formulated to address the unmet needs in this field, with introduction of direct oral anticoagulants (DOACs) especially factor Xa inhibitors like rivaroxaban, apixaban, edoxaban, betrixaban and dabigatran with their own set of challenges in terms of higher costs, risk factors and lack of a reversal agent in case of emergencies.
Most of the research efforts in the anticoagulation industry are now being directed at finding novel solutions to overcome the limitations posed by existing medication, with companies developing anticoagulant reversal agents, precision molecular modelling and using novel approaches like taurolidine technology.
Here are some companies in the anticoagulation field that are developing some cutting-edge drugs and technology and redefining the therapeutics space.
Portola Pharmaceuticals (NASDAQ: PTLA)
Market Cap: $ 1.81B; Current Share Price: 27.24 USD
Data by YCharts
This biopharmaceutical company aims to develop and commercialize first-in-class therapeutics for the treatment of thrombosis and hematologic diseases. The company product line includes Andexxa® [coagulation factor Xa (recombinant), inactivated-zhzo], the only FDA approved anti-dote for rivaroxaban and apixaban when anticoagulation needs to be reversed due to uncontrolled bleeding and Bevyxxa® (betrixaban), an oral factor Xa inhibitor for patients hospitalized in cases of severe illness.
Image Source: https://www.portola.com/medicines/
The company has a very robust network of collaborations and partnerships such as nonexclusive clinical collaboration agreements with all Xa inhibitor manufacturers. Portola has worldwide commercial rights for andexanet alfa, excluding Japan. It has entered into agreements with Bristol-Myers Squibb and Pfizer, Bayer and Janssen and Daiichi-Sankyo for including cohorts dosed with the approved Factor Xa inhibitors such as apixaban, rivaroxaban and edoxaban respectively during its Phase II trials.
In Japan, Bristol-Myers Squibb and Pfizer have the rights over development, regulatory and commercial aspects of operations in the manufacture and commercialization of andexanet alfa as a universal antidote for Factor Xa inhibitors. This is in addition to the tie-up with Bayer and Daiichi Sankyo for using their Factor Xa inhibitors, rivaroxaban and edoxaban in clinical trials.
The company also holds global rights over cerdulatinib, a Syk/JAK inhibitor for the treatment of hematologic cancers such as T-cell lymphoma (PTCL), follicular lymphoma (FL) and inflammatory diseases etc. and its non-topical formulations including oral formulations. Cerdulatinib has received Orphan Drug Designation by the FDA for the treatment of peripheral T-Cell lymphoma. It is also evaluating PRT2761 its lead sky inhibitor candidate in collaboration with Ora, Inc. for treatment of allergic conjunctivitis.
The company has submitted a Prior Approval Supplement (PAS) to FDA for large-scale manufacturing of Generation 2 Andexxa. It also received a new technology add-on payment for Andexxa.
As per the companies Q3 financial results, cash, cash equivalents and investments as on September 30, 2018 totalled $380.9 million, as compared to $534.2 million as on December 31, 2017. Revenue for the period stood at $14.2 million, compared with $3.8 million for the third quarter of 2017. Portola reported a net loss of $71.3 million, or $1.08 net loss per share, compared with a net loss of $82.9 million, or $1.41 net loss per share, for the same period in 2017.
A report by Zack investment Research states that the company is estimated to have sales of $10.43 million for the current fiscal year as compared to $9.80 million during the same quarter of 2017, a growth of 6.4%.
The company was recently acquired by AMAG Pharmaceuticals, Inc. (NASDAQ: AMAG), primarily for its Ciraparantag (PER977), a drug used for reversing the anticoagulant effects of novel oral anticoagulants (NOACs) or low molecular weight heparin (LMWH), in case of uncontrolled bleeding, to re-establish normal clot formation. The FDA has conferred a Fast Track review designation for Ciraparantag and a composition of matter patent protection until 2034 by the USPTO.
The Anticoagulant Reversal agent, a synthetic small molecule, is indicated for use in completely reversing and sustaining the effects for 24 hours for anticoagulants such as Daiichi Sankyo Co. Ltd.’s Savaysa™ /Lixiana® (edoxaban), Johnson & Johnson’s and Bayer HealthCare AG’s Xarelto® (rivaroxaban) and Bristol-Myers Squibb Company’s and Pfizer Inc.’s Eliquis® (apixaban).
The company is also developing Felbamate (PER726) for treatment of Super-Refractory Status Epileptics (SRSE). It has applied for patent for a novel concentrated, formulation of felbamate suitable for IV administration. It is also conducting pre-clinical studies for Glucagon for treatment of (Hypoglycemia).
According to a press release by AMAG, some of the aspects of the acquisition are as follows: AMAG paid the Perosphere equity holders $40 million in cash consideration (subject to customary purchase price adjustments) net of approximately $10 million due to AMAG under a convertible note that Perosphere issued to AMAG in October 2018. AMAG also repaid $12 million of Perosphere’s term loan indebtedness and assumed $6.2 million of Perosphere’s other liabilities.
Perosphere equityholders will be eligible to receive regulatory milestones of up to $140 million, inclusive of a $40 million milestone payment upon approval by the European Medicines Agency, if the final U.S. label has no boxed warning. Perosphere equityholders are also eligible to receive commercial sales milestone payments of up to an aggregate of $225 million. The first sales milestone payment of $20 million would be payable upon achieving annual net sales of $100 million.
Verseon Corporation (LSE: VSN.L)
Market Cap: GBp 145.59M; Current Share Price: 96.00 GBp
The company’s innovative proprietary drug discovery platform is the first computationally driven solution for precision molecular modelling for fast and cost-effective innovations. The company aims to leverage this platform to target diseases such as diabetic macular edema, hereditary angioedema, and oncology (solid tumors). Anticoagulation is one of the company’s primary focus areas.
Verseon aims to reduce the gap between R&D to commercialisation stage by using its platform to accurately model molecular interactions, generate optimization algorithms and use technology to integrate synthetic and medicinal chemistry knowledge. It can consistently design and synthesize drugs hitherto not possible through conventional methods.
Image Source: https://www.verseon.com/platform/overview
The company uses its trifecta of Molecule Creation Engine, Molecule Modeling Engine and Laboratory Integration to shortlist the ones with the most potential for synthesis, laboratory testing, and optimization.
The company is currently holding pre-clinical and Phase I trials for candidates such as an oral anticoagulant for use in cardiovascular anomalies, Kallikrein inhibitors for diabetic macular edema, hereditary angioedema and angiogenesis inhibitors for solid tumors.
The company predicts an annual world market for anticoagulant drugs to reach $24 billion per year per annum, while for Hereditary angioedema (HAE) the market is expected to be worth $3.8 billion in 2025.
Image Source: https://www.verseon.com/programs/overview
As per its interim results, the company had submitted phase I protocol for lead Precision Oral Anticoagulants (PROACs) VE-1902 and second PROAC, VE-2851, is in CMC scale-up for kgs of material and is expected to enter clinical trials in 2019.
As of June 30, 2018, total assets were $68.3 million, including cash, cash equivalents, and short-term investments of $19.2 million. The company also closed a mortgage of $22.2M for laboratory and administrative facility.
The company also owns BlockRules Ltd., its subsidiary that develops blockchain technology for tokenized securities that aims to transform drug development funding models.
CorMedix (NYSE: CRMD)
Market Cap: $ 180.08M; Current Share Price: 1.71 USDData by YCharts
It is a biopharmaceutical company, that focuses on taurolidine technology, for prevention and treatment of infectious and inflammatory diseases. The company has received a fast track status and a Qualified Infectious Disease Product (QILP) for its lead product candidate Neutrolin®, a non-antibiotic microbial solution for preventing bloodstream infections arising out of the use of central venous catheters.
In addition, the company is using its taurolidine technology to build an array of antimicrobial medical devices for areas such as surgical sutures, meshes and topical hydrogels. Neutrolin® is approved as a CE marked medical device in Europe.
Image Source: http://www.cormedix.com/research-development/
CorMedix is aiming to use its taurolidine technology for rare paediatric cancers.
The company recently closed a $7.5 million, secured convertible debt financing, having a three-year maturity period and interest rate of 10% per annum with an option to convert it into the company’s common stock at a conversion price of $1.50 per share. The company proposes to use these funds for the development of Neutrolin®.
As per the company’s Q4 financial results, cash on hand and short-term investments as on September 30, 2018 was $6.4 million.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.