07 Feb CAN GENE THERAPY AND RNA TECHNOLOGY COMBAT CYSTIC FIBROSIS?
Cystic Fibrosis is a chronic genetic disorder of the mucus glands that affects 2,500 newborns each year in the U.S. 30,000 people are currently affected by this disease and about 1 in 20 or roughly 12 million Americans are carriers of the “CF” gene and are unaware of their condition according to the Centers for Disease Control and Prevention.
There is no permanent treatment for this condition. Efforts are limited to alleviating the symptoms and slowing down the progression of the disease, which has resulted in an increase in the lifespan of the affected to 30 years from being nearly fatal.
The treatment for cystic fibrosis mainly consists of reducing the mucus blockage of the lungs by physical therapy (postural, bronchial drainage), exercise and therapeutics. Medicinal options usually consist of aerosolized bronchodilators, CFTR Modulators, Pancreatic enzyme supplements, mucolytics and decongestants.
Ongoing research in the field is trying to address the unmet needs for a long-term and safe solution for tackling this disease. Companies are creating breakthrough technological innovations such as Gene therapy, rectifying the chloride transport defect in cells, improving diagnostic tools, etc.
There is a huge potential for growth in the cystic fibrosis treatment market which is indicated by the projection that the industry will be worth USD 13.9 billion by 2025, according to a research report by Grand View Research, Inc.
The market will see tremendous progress in the future owing to innovations by companies such as gene therapy, RNA technology, Protein targeting and novel administration methods.
Translate Bio (NASDAQ: TBIO)
Market Cap: $ 250.09M; Current Share Price: 5.54 USD
Translate Bio is a mRNA focused biotechnology company that aims to transform the protein and gene dysfunction disease space. Its proprietary mRNA platform (MRTTM), can deliver encoded functional proteins to dysfunctional cells thereby restoring their functionality and balance.
The company which was hitherto known as RaNA Therapeutics acquired the messenger RNA (mRNA) therapy platform from Shire plc, to enhance its ability to correct a wide array of disease genotypes irrespective of mutations and overcome its limitations in accessing new targets. The company acquired Shire plc’s programs in cystic fibrosis and ornithine transcarbamylase (OTC) deficiency, a urea cycle disorder.
As part of its drug development initiative, the company has two lead programs namely mRNA therapy for cystic fibrosis that seeks to restructure the CFTR pathway and restore its ability to produce healthy protein by replacing the defect in the CFTR gene irrespective of the type of mutation and OTC protein production in the liver for treating Ornithine transcarbamylase (OTC) deficiency, a singular genetic metabolism defect and a common urea-cycle disorder.
The Investigational New Drug Application (IND) submission for MRT5201 is currently on hold by the FDA for want of more clinical and non-clinical information, which the company seeks to address and bring to a quick resolution.
The company is also trying to leverage its mRNA technology platform for targeting disease in areas such as CNS disorders, ocular diseases and blood disorders. Its initial efforts are targeted towards restoring the expression of intracellular and transmembrane proteins, a relatively unexplored area with a huge unmet need.
The company has a licensing and collaboration agreement with Sanofi Pasteur for development of mRNA vaccines for up to five infectious disease pathogens. It received a $45 million upfront payment from Sanofi in lieu of the same.
In the pipeline are MRT5005, which can deliver mRNA encoded fully functional cystic fibrosis transmembrane conductance regulator (CFTR) protein to the lung. It received an orphan drug designation by the FDA in 2015 and is currently in clinical trials.
MRT5201 for the treatment of OTC deficiency, and several other discovery stage programs to identify mRNA product candidates for diseases related to lungs, liver, eye, CNS and lymphatic systems.
As per its Q3 financial results, Translate Bio had $161.1 million in cash, cash equivalents and investments as on September 30, 2018.
Arcturus Therapeutics (NASDAQ: ARCT)
Market Cap: $ 54.04M; Current Share Price: 5.06 USD
Arcturus is using its RNA medicine expertise to develop novel therapeutics in rare, liver and respiratory diseases. The company has manufacturing proficiency in RNA Drug Substance & LUNAR® Nanoparticle Drug Product which it is using for development of a protein replacement therapy that can restore functionality and balance to the affected organs.
Arcturus is developing a CFTR functional corrector that can deliver an encoded functional CFTR into the lungs directly irrespective of its genotype. This action can reduce mucus accumulation, tissue scarring and arrest the progression of respiratory dysfunction. The company is planning to submit an Investigational new drug application (IND) for LUNAR –CF in 2020. In addition, it has a second platform based on the ligonucleotide chemistry technology called Unlocked Nucleomonomer Agent (UNA) that can decrease off-target effects and increase duration of action in siRNA medicines.
It has seven programs currently under various stages of development with companies such as Cystic Fibrosis Foundation Therapeutics, Inc. for the treatment of cystic fibrosis, agreement with CureVac AG for developing mRNA therapeutic candidates to treat ornithine transcarbamylase (OTC) deficiency , collaboration with Ultragenyx to develop up to ten mRNA therapeutic candidates including Glycogen Storage Disease type III.
The company is using its proprietary LUNAR lipid-mediated delivery system, to develop self-amplifying RNA-based vaccines and therapeutic for human and veterinary use in association with Synthetic Genomics. It has partnered with Janssen Pharmaceuticals, Inc., a Johnson & Johnson company, for treatment of HBV infections and other diseases. It has tied up with Takeda Pharmaceutical Co. Ltd for developing mRNA candidates for nonalcoholic steatohepatitis (NASH) and other gastrointestinal disorders using its LUNAR drug delivery platform.
The company has a strong intellectual property rights portfolio consisting of 140 Patents & Patent Applications issued in US, EU, JP, China and Other Countries.
As per the Q3 financial results, the company had cash, cash equivalents, and investments amounting to $32.8 million as on September 30, 2018, including proceeds from a $10 million Loan and Security Agreement with Western Alliance Bank.
SAVARA (NASDAQ: SVRA)
Market Cap: $ 258.2M; Current Share Price: 7.35 USD
SAVARA’s area of interest is rare lung diseases with unmet needs. The company is developing a portfolio of products targeted towards an array of illness by developing/acquiring novel product candidates and successfully advancing them to approvals and commercialization.
The company’s lead drug candidate for the treatment of cystic fibrosis is AEROVANC (vancomycin hydrochloride inhalation powder), an inhaled dry powder form of vancomycin to treat Methicillin-resistant Staphylococcus aureus (MRSA) lung infection, that seeks to fill the gap in the market for an inhaled MRSA antibiotic.
Savara is in preparation for Phase 3 trials for Vancomycin, which can be directly delivered to the site of infection in the lungs improving its efficacy and minimal side-effects owing to lower systemic drug exposure as compared to IV antibiotic treatment.
The company has other drugs in the pipeline such as Molgradex, an inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF), which is in Phase 3 development for autoimmune pulmonary alveolar proteinosis(aPAP), Phase 2a development stage for nontuberculous mycobacteria lung infection and in preparation for Phase 2a development in cystic fibrosis.
In its quest to build a portfolio of first-in-class products, the company has acquired aerosolized amikacin/fosfomycin, a proprietary combination antibiotic that is phase 2 ready, and has demonstrated potent and broad-spectrum antibacterial activity against highly drug resistant pathogens.
Molgradex has been awarded an orphan drug designation by the FDA in the U.S and the E.U, for the treatment of PAP, while AeroVanc has been granted Orphan Drug Designation and Qualified Infectious Disease Product (QIPD) status for the treatment of persistent MRSA lung infection in the U.S and E.U.
The company has also partnered with the PAP foundation to extend support for patient education and expand the patient registry.
As per the Q3 financial results, the company reported cash, cash equivalents & short-term investment securities amounting to ~$112.0 million as on September 30, 2018. It also has an outstanding loan and security agreement of $15 million. The company received net proceeds of $45.8 million from a successful public offering.
PROTEOSTASIS THERAPEUTICS (NASDAQ: PTI)
Market Cap: $ 148.17M; Current Share Price: 3.01 USD
A clinical stage biotechnology company, Proteostatis is developing small molecule therapeutics to treat cystic fibrosis by targeting dysfunctional proteins.The company’s key area of research is the Proteostasis Network (PN) that ensures that every protein performs its designated function or is degraded to prevent damage. However, owing to certain factors the network becomes dysfunctional and leads to malfunctioning of organs or build up of toxicity in the body causing profound damage.
Proteostasis is developing an innovative therapeutic that can control or rebalance the PN by enhancing the ability of the dysfunctional PN to control or delay the progression of disease.
The company’s proprietary Disease-Relevant Translation (DRT™) platform brings together genomics, proteomics and functional assays with medicinal chemistry and systems biology to capitalize on the emerging knowledge of the PN for channeling it into therapeutics that address unmet needs.
The company’s lead drug candidate for cystic fibrosis uses a three pronged strategy to combat CF, by combining PTI-428, an investigational CFTR amplifier, PTI-801, an investigational CFTR corrector and PTI-808, an investigational CFTR potentiator that can increase CFTR protein level, correct the dysfunctional protein and enhance the functioning of mutated F508del CFTR in clinical tests. FDA has granted the company a Fast Track Designation for its triple combination program.
It is collaborating with Astellas Pharma Inc., to realize the potential of unfolded protein response (UPR) pathway, a mechanism that is activated to provide proper cellular stress response in protein conformational disorders. The company has entered into a worldwide licensing agreement with Genetech, a member of the Roche Group, for a potential therapeutic small molecule modulator of an undisclosed target within the proteostasis network, for an upfront payment of $100 million, in addition to tiered royalties from sale of the medicines in the event of successful commercialization.
As per its Q3 financial results, the company has cash, cash equivalents and short-term investments of $46.4 million as on September 30, 2018, including net proceeds of approximately $80.0 million from a follow-on offering, The Company also reported net proceeds of about $11.2 million from sales under an ATM program.
Market Cap: $ 8.63M; Current Share Price: 0.175 USD
The company is using its proprietary iSPERSE technology platform to develop inhaled therapeutics for chronic pulmonary illnesses. iSPERSE (inhaled small particles easily respirable and emitted) is a dry powder technology that can enhance local drug concentrations with nominal side-effects. The technology seeks to overcome the limitations of traditional therapeutics having lactose blend and metered dose inhalation.
iSPERSE does not need a carrier making it suitable for low or high drug load therapeutics. The manufacturing process is easily reproducible and scalable. It exhibits consistency in flow rate with minimal patient variability and can deliver antibodies, peptides and nucleic acids. It is compatible with a variety of inhalers and has a robust safety profile.
The company’s pipeline includes PUR1900, a first-in-class Pulmazole anti-fungal product candidate for treating allergic bronchopulmonary aspergillosis (ABPA) in severe asthma and cystic fibrosis, PUR1800 a narrow-spectrum kinase inhibitor (NSKI) licensed from Respivert, a subsidiary of Janssen Pharmaceuticals for treatment of acute exacerbations of COPD (AECOPD), PUR5700, narrow-spectrum kinase inhibitor (NSKI) for prevention or treatment of AECOPD, acute asthma and IPF and PUR0200 an inhalable iSPERSE™ reformulation of tiotropium bromide for COPD patients being developed as a branded generic of Spiriva HandiHaler.
The company has received a FDA Qualified Infectious Disease Product (QIDP) designation obtained for ABPA and CF. Its platform enjoys intellectual property protection till 2030.
The company recently made a public offering of 1,561,177 shares at a price to the public of $0.17 per share and expects to receive gross proceeds of approximately $265,400 from the offering. According to the company, it also made a securities purchase agreement with an institutional investor, providing for the purchase and sale of 9,375,000 shares of common stock at a price of $0.32 per share in a registered direct offering, resulting in total gross proceeds of $3.0 million.
As per its Q3 financial results, as on September 30, 2018, Pulmatrix had $3.8 million in cash and cash equivalents, compared to $3.6 million as on 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.