03 Jun Research in Biologics and Small Molecules aim to unravels the genetics of Systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE) is an autoimmune disease that causes the body’s immune system to attack healthy tissue causing inflammation, photosensitivity, oral ulcers, pleuritis, joint pain, arthritis, fever and a butterfly rash. In the long-run it can affect the kidneys, brain and heart as well. The disease is asymptomatic and has no identified cause or cure. The current treatment options aim at alleviating the symptoms and improving the quality of life of those affected and includes the use of glucocorticoids, antimalarial agents, topical steroids and NSAIDS for pain management.
It takes an average of 6 years from developing the symptoms of lupus to being diagnosed according to data made available by the lupus foundation of America. This chronic condition which affects an estimated 1.5 million people in America each year costs over $21,000 in annual financial costs. Another report by the Centres for Disease Control and Prevention estimates that 16,000 new diagnosis of Lupus are made each year.
According to a report by Grand View Research the lupus treatment market is set to reach USD 3.08 billion by 2025 growing at a CAGR of 7%. GSK’s Benlysta (belimumab), is currently the only biologic therapy approved by the FDA for the treatment of lupus. It was recently approved for use in children and adolescents as well. The development of new therapies ranging from biologics, JAK inhibitors to stem cell transplantation will be a key driver of growth in the market. The prohibitive cost of treatment and the lack of insurance coverage might act as hurdles to growth.
We take a look at some companies that are researching novel mechanisms to help treat this hitherto incurable disease.
Corbus Pharmaceuticals (NASDAQ: CRBP)
Market Cap: $475.04M; Current Share Price: 7.37 USD
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Corbus is engaged in creating innovative therapies for the treatment of inflammatory and fibrotic diseases by harnessing the potential of the endocannabinoid system. This clinical stage company is developing lenabasum as its lead candidate for the treatment of Systemic Lupus Erythematosus, which is currently undergoing Phase II trials.
Lenabasum is a synthetic small molecule selective cannabinoid receptor type 2 (CB2) agonist that targets chronic inflammation and fibrotic processes. It has shown to promote the production of Specialized Pro-resolving lipid Mediators (“SPMs”) that activate the endogenous pathways which help treat inflammation and achieve bacterial clearance without the need for immunosuppression. It can also limit fibrogenic growth factors that can prevent tissue fibrosis (scarring).
Its pipeline consists of lenabasum which is being developed for the treatment of systemic sclerosis, dermatomyositis, and systemic fibrosis. In addition, it is studying the efficacy of CBR-4001, a second-generation, peripherally restricted, CB1 inverse agonist for the treatment of organ specific fibrosis including liver, kidney, heart and lung. This candidate will enter phase I trials in 2019 with NIH committing to fund its Phase II studies. It has built a preclinical library of an impressive 600 compounds, which it intends to translate into at least 2 phase I programs each year.
Its proprietary technology is safe guarded by a robust Intellectual Property Rights (IPR) portfolio including 4 U.S patents covering composition of matter and broad use in inflammatory and fibrotic diseases that offer it protection through 2034.
In September 2018, the company entered into a licensing agreement with Jenrin Discovery, LLC for gaining the exclusive worldwide rights to more than 600 novel compounds targeting the endocannabinoid system. It has also entered into collaboration with Kaken Pharmaceutical Co., Ltd (TYO: 4521) for the development and commercialization of lenabasum in the Japanese market, in consideration for a $27 million upfront payment and over $173 million in milestone payments and double-digit royalties.
As per its 2018 year-end financial results, the company had $41.7 million in cash and cash equivalents as of December 31, 2018. Additionally it completed a public offering of common stock for gross proceeds of $40 million.
Gilead Sciences (NASDAQ: GILD)
Market Cap: $83.06B; Current Share Price: 65.15 USD
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Its lead candidate for the treatment of lupus is GS-9876 a Syk inhibitor that is currently undergoing phase I clinical trials. Spleen tyrosine kinase (SYK) has the ability to regulate immunoreceptor signaling and is crucial for B lymphocytes, monocytes, macrophages, dendritic cells, and osteoclasts cell activation. It has been identified as a key factor in setting off and aiding progression of autoimmune disease such as rheumatoid arthritis (RA) and lupus. GS-9876 demonstrated biomarker changes in clinical studies along with improved safety profile and tolerability.
Gilead also offers a chimeric antigen receptor T cell therapy for adult patients with relapsed or refractory large B-cell lymphoma named Yescarta, a kinase inhibitor called Zydelig, an oral formulation of an endothelin receptor antagonist indicated for use in pulmonary arterial hypertension named Letairis and an antifungal agent called AmBisome to name a few. The company has an extensive pipeline consisting of numerous candidates under development for treatment of disorders such as HIV/AIDS, Liver diseases, Hematology and Oncology, Cardiovascular and Inflammatory or Respiratory disorders.
It has a strong network of strategic collaborations with companies such as Bristol-Myers Squibb Company (NYSE: BMY), Janssen Sciences Ireland UC, Japan Tobacco (TYO: 2914), Galapagos NV (NASDAQ: GLPG), Scholar Rock Holding Corporation (NASDAQ: SRRK), Tango Therapeutics, Pfizer (NYSE: PEE), Sangamo Therapeutics (NASDAQ: SGMO), Gadeta B.V, HiFiBiO Therapeutics, Agenus (NASDAQ: AGEN), and Insitro Inc.
Resolve Therapeutics (Private)
Resolve’s lead candidate for the treatment of lupus is RSLV-132, a mono-specific nuclease Fc-fusion protein that eliminates immune complexes, inhibits the activation of interferon and restores the damage caused to kidneys. This biopharmaceutical company’s sole focus is on unmet medical needs in the treatment of systemic lupus erythematosus (SLE) and sjögren’s syndrome. It has leveraged upon the insights offered by scientific advancements and research in the molecular basis of these diseases to forge a novel approach to treating lupus and sjögren’s syndrome.
RSLV-133 eliminates RNA, one of the primary causes of inflammation in both lupus and sjögren’s syndrome and helps decrease inflammation and its impact on other organs. The candidate has demonstrated positive impact in a single dose safety study in 32 healthy volunteers and a multi-dose safety study in 32 patients with SLE. The company is currently engaged in enrolling patients for a phase 2 SLE study with active skin disease and elevated RNA autoantibodies.
In addition, it is also developing RSLV-133; a bi-specific Fc-nuclease fusion protein encompasses two different nuclease activities into one drug molecule.
Aurinia Pharmaceuticals (NASDAQ: AUPH)
Market Cap: $580.20M; Current Share Price: 6.30 USD
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It is developing an investigational drug voclosporin to be used as a potential treatment for lupus nephritis (LN). In addition, the company is also looking at using voclosporin as a topical ophthalmic solution for the treatment of dry eye disease and focal segmental glomerularsclerosis (FSGS). Voclosporin’s unique binding action induces structural changes in calcineurin and increases immunosuppressive activity. It is a best-in-class calcineurin inhibitors (CNI) with a dual mechanism of action that can not only block IL-2 expression and T-cell mediated immune responses but also stabilizes the podocyte in the kidney.
Volcosporin has shown to be more effective than conventional calcineurin inhibitors (CNI) by demonstrating a more stable pharmacokinetic and pharmacodynamic interplay and improved metabolic profiles. The company is engaged in Phase III clinical trials named AURORA, which are Phase 3 global placebo-controlled clinical trial to assess voclosporin for the treatment of active lupus nephritis. Its AURA-LV (AURA), a global placebo controlled Phase 2 study that aims to evaluate whether voclosporin added to mycophenolate mofetil (MMF) could increase speed of remission and overall remission rates in the presence of low doses of steroids has the distinction of being the first such trial in lupus nephritis to meet it primary endpoints.
The company has received a shot in the arm as the USPTO has granted a Notice of Allowance to the company for patenting voclosporin’s method of use and dosing protocol for lupus nephritis (LN) under U.S. patent application 15/835,219, entitled “PROTOCOL FOR TREATMENT OF LUPUS NEPHRITIS”. This could enable the company to stave off competition from generics at least until 2037.
As of December 31, 2018, its cash, cash equivalents and short-term investments were at $125.9 million. The company closed an At-the-Market (ATM) offering for the sale of 4,608,409 shares at $6.55 a share for gross proceeds of $30 million in November 2018.
Nektar Therapeutics (NASDAQ: NKTR)
Market Cap: $ 5.62B; Current Share Price: 32.26 USD
Data by YCharts
Nektar’s focus areas are cancer, auto-immune disease and chronic pain, where the company seeks to make an impact with its novel polymer chemistry platform. The company’s lead drug candidate for treatment of lupus is an Anti-CD40L named Dapirolizumab Pegol which it is developing in partnerhip with Biogen (NASDAQ: BIIB) and UCB (EBR: UCB)
CD40L is a protein found in B and T cells that help regulate the immune system. Anti-CD40L has the ability to block CD40L and reduce the disease activity in those affected. It is currently undergoing Phase II clinical trials to test its efficacy and safety in patients with moderately to severely active systemic lupus erythematosus.
Nektar is the go-to company for clinical collaborations, co-development and licensing agreements with top-notch biotechnology and pharmaceutical companies such as Astra Zeneca (NYSE: AZN), Bristol-Myers Squibb, Amgen (NASDAQ: AMGN), Shire (LSE: SHRS), Halozyme (NASDAQ: HALO), Roche (SWX: ROG), Pfizer, Eli Lilly (NYSE: LLY) and Takeda (NYSE: TAK) to name a few, that use the company’s platform technologies to develop next-generation therapeutics.
In addition, the company has a pipeline of over 10 new drug candidates such as NKTR-181 for chronic low back pain, NKTR-214 in combination with OPDIVO(nivolumab) for Melanoma , Renal Cell Carcinoma, Immuno-Oncology and Urothelial Cancer( in partnership with Bristol- Myers Squibb),PEGPH20 for pancreatic cancer (in partnership with Halozyme), NKTR-214 in combination with TECENTRIQ(atezolizumab) or KEYTRUDA(pembrolizumab), NKTR-358 for Auto Immune disease (in partnership with Lilly), NKTR-262 in combination with NKTR-214 , NKTR 214 in combination with TAK-659 ( in collaboration with Takeda) and NKTR-255 for immune-oncology.
The company also has licensing agreement with Astra Zeneca for Movantik in lieu of which it will receive escalating royalties on sales and milestone payments. It also has collaboration with Baxalta a subsidiary of Shire plc, for development of ADYNOVATE™ indicated for treatment of Hemophilia A in exchange for royalties and milestone payments.
As per its 2018 year-end financial results, cash and investments in marketable securities were $1.9 billion as on December 31, 2018 as compared to $353.2 million in December 31, 2017.
Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.
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