Nerve growth factor(Amgen, Inc.)

Current pain medications are addictive (opioids), or potentially damaging to the liver (acetaminophen/Tylenol or kidneys with substantial gastrointestinal toxicity (nonsteroidal anti-inflammatory drugs, NSAIDs). Three notable events in November 2022 underscore the need for innovation in safer pain treatment First, in its updated Clinical Practice Guidelines for Prescribing Opioids, the Centers for Disease Control and Prevention (CDC) encourages physicians to again use opioids in individualized cases for moderate-to-severe acute and chronic pain, responding to a crisis of untreated pain leftover from its prior 2016 guidelines. Second, Regeneron announced that it stopped developing its nerve growth factor (NGF) inhibitor for knee and hip osteoarthritis (OA) pain in a Phase 3 trial. This follows cases of a rapidly progressive form of OA that required joint replacement. Pfizer also discontinued its NGF program for pain in 2021 due to similar safety concerns and unproven pain efficacy over NSAIDs alone. Targeting NGF for pain never made much sense scientifically, as it has a poor pain mechanism of action. Moreover, developing an antibody therapy – rather than a small molecule for the pain space – leaves unanswered how limited U.S. healthcare dollars would absorb the costs for an ailment affecting more than 50 million Americans. And third, Australian regulators are considering restricting the sale of acetaminophen this month after an independent expert report raised concern about overdoses in teenagers, females at the highest risk. The proposals include limiting the amount bought over the counter so that it is not ‘stockpiled’ at home and requires a prescription for those under 18 years of age. Acetaminophen’s liver toxicity risk Acetaminophen has a narrow therapeutic index, and hepatotoxicity is a significant risk with deliberate overuse (e.g., suicide attempt) and unintentional overuse (e.g., consuming acetaminophen without realizing it is present in various prescription and over-the-counter formulations). Furthermore, its use in patients with compromised liver function, particularly in the elderly, poses a significant risk for liver injury. Despite ongoing regulatory and educational efforts over the past several years to improve patient safety, intentional and unintentional acetaminophen overdose remains an essential public health problem. Every year in the U.S, around 30,000 patients are hospitalized due to acetaminophen hepatotoxicity. A safer, non-NSAID alternative to acetaminophen is needed to address acetaminophen hepatotoxicity. Indeed, similar to the discussions currently happening in Australian Regulators, a decade ago the FDA issued a boxed warning highlighting the potential for severe liver injury. In Canada, acetaminophen toxicity persisted despite labeling changes implemented in 2009 and 2016. These labeling standards were made to communicate the dangers of acetaminophen overdose and promote safe use. However, monthly rates of hospital and intensive care unit admissions for accidental acetaminophen overdose were unchanged between April 2004 and March 2020. Kidney, cardiovascular and gastrointestinal (GI) risks with NSAIDs Risks from overuse of NSAIDs include elevated blood pressure, renal toxicity leading to acute kidney injury (AKI) and GI damage. Indeed, most chronic NSAID users have significant small-intestine damage and bleeding. In treating acute pain in the post-operative period, NSAIDs use leads to AKI and complications in patients undergoing surgery. There are several patient populations at risk of NSAID-induced AKI. Patients vulnerable to NSAIDs’ renal toxicity leading to serious adverse outcomes include patients with chronic kidney disease. NSAID exposure was associated with an approximate 1.6-fold rise in the odds of developing AKI in hospitalized pediatric patients and in older people. Prevalence of pain and Opioid Use Disorder (OUD) in the U.S. OUD affects 2.1 million people in the U.S., 16 million people worldwide, and over 120,000 deaths annually attributed to opioids. OUD includes the misuse of prescription pain relievers and the use of heroin. Prescription pain reliever misuse was the second most common form of illicit drug use in the U.S. in 2018, after marijuana use, with 3.6% of the population misusing pain relievers. In the U.S., pain affects more adults than diabetes and cancer, combined with an estimated cost to the healthcare system of $635 billion/year. In September 2022, the CDC released preliminary data that drug overdose deaths exceeded 107,000 in the preceding year, the most significant single-year increase. Drug deaths were disproportionately higher in the younger population than in the older population. Though opioid prescriptions have been declining since 2012, and most overdose deaths are now from fentanyl sold on the street, often laced with other drugs, 14,000+ of these deaths were from prescription painkillers. Additionally, 500,000 emergency visits per year are attributed to misuse of prescription pain killers. Future pain relief innovation Multiple randomized clinical trials have shown that combination non-opioid therapies (large doses of acetaminophen and NSAIDs) are at least as effective as opioids for many common types of moderate to severe pain. Though pain is subjective, multiple well-conducted clinical trials have demonstrated the high reproducibility of clear endpoints. Hence, pain clinical trials have a track record of demonstrating efficacy when they are well designed and executed. The prevalence of OUD, including high rates of overdose in the U.S. and toxicity profiles of currently available medications, underscore the need for a new strategy. Recognizing the need for novel non-opioid therapies, the National Institutes of Health (NIH) established the Helping to End Addiction Long-Term (HEAL) Initiative in 2018. This program’s financial, scientific, and commercialization support is an essential start toward pain relief innovation. The future towards the safer treatment of pain will come as biopharma, and investor communities appreciate the significant opportunities in supporting scientifically rigorous and clinically validated lead assets for the safer treatment of pain.

PRINCETON, N.J., June 03, 2021 (GLOBE NEWSWIRE) -- Oyster Point Pharma, Inc. (Nasdaq: OYST), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies to treat ocular surface diseases, today announced the expansion of its pipeline with the introduction of Enriched Tear Film (ETF™) Gene Therapy and proof-of-concept in vivo study results from its first gene therapy candidate, OC-101. ETF™ Gene Therapy is a proprietary adeno-associated virus (AAV) based gene therapy approach where a target gene is delivered to human lacrimal gland cells via intralacrimal gland injection. Rather than replacing a gene that is defective or missing, a new target gene is delivered that may potentially produce a selected naturally occurring protein, enzyme, or other therapeutic gene product. The goal for this target gene is to produce a selected gene product to change cell behavior and function on the ocular surface. Oyster Point’s investigational drug, OC-01 (varenicline) nasal spray, a highly selective cholinergic agonist, may play a role in ocular surface diseases treated with ETF™ Gene Therapy through its potential to modulate the secretion of a selected gene product. In this proof-of-concept in vivo study evaluating OC-101 (AAV-NGF), a single, intralacrimal gland injection of an AAV containing the human NGF (hNGF) gene resulted in statistically significant levels of hNGF protein being expressed within the lacrimal gland and tear film of a rabbit model, as compared to control. hNGF was secreted into the tear film as early as Day 7, after the intralacrimal gland injection. No control animals showed evidence of hNGF in the lacrimal gland or tear film. Additionally, three weeks following OC-101 (AAV-NGF) transduction of the lacrimal gland, cholinergic activation of the lacrimal gland with OC-01 (varenicline) nasal spray resulted in statistically significant increases in hNGF expression in the tear film, as compared to pre-cholinergic stimulation levels and as compared to control. After cessation of OC-01 (varenicline) nasal spray, hNGF tear protein levels returned to pre-cholinergic activation levels (measured at Day 14). During the 42-day study, there were no macroscopic or microscopic safety findings observed associated with the intralacrimal gland administration of OC-101 (AAV-NGF) or OC-01 (varenicline) nasal spray. “Oyster Point’s proprietary ETF™ Gene Therapy approach has shown the potential to increase basal levels of NGF in the tear film and sustain NGF secretion onto the ocular surface as a part of the natural tear film,” said Jeffrey Nau, Ph.D., MMS, president and chief executive officer of Oyster Point Pharma. “With additional preclinical studies underway, Oyster Point plans to meet with the U.S. Food and Drug Administration (FDA) for a pre-IND meeting to discuss development of OC-101 (AAV-NGF) for patients with Stage 2 and Stage 3 neurotrophic keratopathy. In addition, Oyster Point will focus its Phase 2 OLYMPIA study of OC-01 (varenicline) nasal spray monotherapy on Stage 1 neurotrophic keratopathy patients.” “We believe that this is the first proof of concept study to show that a cholinergic agonist nasal spray (OC-01) has modulated protein secretion into the tear film after intralacrimal injection of an AAV-based gene therapy,” said Eric Carlson, Ph.D., chief scientific officer of Oyster Point Pharma. “We believe the translated protein may be processed and secreted in the same manner as endogenous proteins in the lacrimal gland by incorporating the proper post-translational modifications and folding. Cholinergic stimulation of the lacrimal gland to increase secretion of tear film components and protein content may represent a potential new approach to treating a number of ocular surface diseases.” Oyster Point Pharma plans to present the proof of concept in vivo data at the upcoming Oyster Point Analyst Day, planned for July 15, 2021. Please use the following link to register for the Analyst Day (). About Oyster Point PharmaOyster Point Pharma is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies to treat ophthalmic diseases. About Enriched Team Film (ETF™) Gene TherapyETF™ Gene Therapy is a proprietary adeno-associated virus (AAV) based gene therapy approach where a target gene is delivered to human lacrimal gland cells via intralacrimal gland injection. Rather than replacing a gene that is defective or missing, a new gene is delivered that potentially may produce a selected naturally occurring protein, enzyme, or other therapeutic gene product. The goal for this target gene is to produce a gene product to change cell behavior and function on the ocular surface. The human lacrimal gland is a seromucous gland that secretes over 1,500 proteins and multiple classes of mucins into the tear film that help protect and nourish the ocular surface.1 It has been shown that when an ocular surface stress occurs, the lacrimal gland responds by up-regulating the production of proteins which are then secreted into the tear film in order to heal the ocular surface.2 The ETF™ Gene Therapy approach intends to leverage this same concept for ocular surface diseases by delivering a target gene to the lacrimal gland to direct the production of the selected gene product that may be secreted in the tear film and then delivered to the ocular surface. In addition, OC-01 (varenicline) nasal spray may play a role in ocular surface diseases treated with ETF™ Gene Therapy through its potential to modulate the secretion of a selected gene product. In ocular surface diseases with inadequate tear film production (such as neurotrophic keratopathy [NK]) and diseases where increased amounts of the selected gene product (such as a protein or enzyme) are required, cholinergic activation of the parasympathetic nervous system with OC-01 (varenicline) nasal spray has the potential to modulate the concentration of the selected gene product. About OC-101 (AAV-NGF) for InjectionAdeno-associated virus (AAV) vectors are nonreplicating DNA delivery vehicles that are currently not known to cause disease. OC-101 (AAV-NGF) is Oyster Point’s investigational gene therapy in development as part of Oyster Point’s proprietary Enriched Tear Film (ETF™) Gene Therapy pipeline expansion. OC-101 (AAV-NGF) is an AAV containing the nerve growth factor (NGF) gene. NGF is a naturally occurring protein secreted by cells on the surface of the cornea and is involved in the differentiation and maintenance of neurons that has been shown to improve corneal nerve architecture and corneal epithelium integrity.3 OC-101 (AAV-NGF) is an investigational gene therapy that has not been tested in humans and has not been approved for any use in any country. The safety and efficacy of OC-101 (AAV-NGF) have not been established. About OC-01 (varenicline) Nasal SprayOC-01 (varenicline) nasal spray is a highly selective cholinergic agonist being developed as a multidose preservative-free nasal spray to treat the signs and symptoms of dry eye disease and neurotrophic keratopathy. The parasympathetic nervous system, the “rest and digest” system of the body, controls tear film homeostasis partially via the trigeminal nerve, which is accessible within the nose. Administered as a preservative-free, aqueous nasal spray, in pre-clinical and clinical studies, OC-01 (varenicline) nasal spray was shown to have a novel mechanism of action with activation of the trigeminal parasympathetic pathway in the nasal cavity to activate natural tear film production. Human tear film is a complex mixture of more than 1,500 different proteins, including growth factors and antibodies, as well as numerous classes of lipids and mucins. This complex tear film is responsible for forming the primary refracting surface of the eye, as well as protecting and moisturizing the cornea. In December 2020, Oyster Point submitted to the U.S. Food and Drug Administration (FDA) a New Drug Application (NDA) for OC-01 (varenicline) nasal spray for the treatment of signs and symptoms of dry eye disease. The Prescription Drug User Fee Act (PDUFA) target action date is October 17, 2021, with a planned U.S. launch of OC-01 (varenicline) nasal spray in the fourth quarter of 2021, if approved by the FDA. OC-01 (varenicline) nasal spray is an investigational new drug and has not been approved for any use in any country. The safety and efficacy of OC-01 (varenicline) nasal spray have not been established. About Neurotrophic KeratopathyNeurotrophic Keratopathy (NK) is a disease characterized by decreased corneal sensitivity and poor corneal healing. The most common causes of corneal sensation loss are viral infection (herpes simplex virus and herpes zoster keratoconjunctivitis) followed by chemical burns, physical injuries, and ocular surface surgery. In addition, systemic diseases such as diabetes and multiple sclerosis may decrease sensory nerve function or damage sensory fibers. NK can be classified broadly into three stages: Stage 1 (mild) consists of ocular surface irregularities and reduced vision, Stage 2 (moderate) exhibits a non-healing persistent defect of the corneal epithelium, and Stage 3 (severe) exhibits corneal ulceration, which may progress to corneal melting and perforation. If not adequately addressed, the progression of NK can lead to vision loss and a breakdown of corneal integrity, can lead to cornea transplantation. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 that reflect the current beliefs, expectations and assumptions of the Company regarding the future of the Company’s business, our future plans and strategies, regulatory approvals, clinical results, future financial condition and other future conditions. All statements other than statements of historical facts contained in this press release, including express or implied statements regarding product candidates, regulatory approvals, planned pre-clinical studies and clinical trials, expected results of pre-clinical studies or clinical trials, and their timing and likelihood of success, expected research and development costs, as well as plans and objectives of management for future operations, are forward-looking statements. The words “if approved,” “may,” “will,” “should,” “would,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplate,” “believe,” “estimate,” “predict,” “potential” or “continue” or the negative of these terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, among other things: the uncertainties inherent in pharmaceutical research and development, including pre-clinical study and clinical trial results and additional analysis of existing data, and the likelihood of our pre-clinical studies and clinical trials demonstrating the safety and efficacy of our product candidates, and other positive results; the timing of initiation of our future clinical trials, and the reporting of data from our current and future trials; the timing or likelihood of regulatory filings and approvals for our product candidates; our ability to obtain and maintain regulatory approvals of our product candidates; our plans relating to commercializing our product candidates, if approved; the success of competing therapies that are or may become available; the beneficial characteristics, safety, efficacy and therapeutic effects of our product candidates; our plans relating to the further pre-clinical and clinical development and manufacturing of our product candidates, including additional indications which we may pursue; the prevalence of dry eye disease and neurotrophic keratopathy and the size of the market opportunity for our product candidates; the expected potential benefits of strategic collaborations with third parties and our ability to attract collaborators with development, regulatory and commercialization expertise; our ability to recruit and retain key personnel needed to develop and commercialize our product candidates, if approved, and to grow our company; existing regulations and regulatory developments in the United States and other jurisdictions; our plans and ability to obtain or protect intellectual property rights, including extensions of existing patent terms where available; our continued reliance on third parties to conduct additional clinical trials of our product candidates, and for the manufacture of our product candidates for pre-clinical studies and clinical trials; the accuracy of our estimates regarding expenses, future revenue, capital requirements and needs for additional financing; our financial performance; market conditions; the sufficiency of our existing capital resources to fund our future operating expenses and capital expenditure requirements; and other risks described in the “Risk Factors” section included in our public filings that we have made and will make with the Securities and Exchange Commission. The Company is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. 1 Dartt, D. A. (2009). Neural regulation of lacrimal gland secretory processes: relevance in dry eye diseases. Progress in retinal and eye research, 28(3), 155-177.2 Wilson, S. E., Liang, Q., & Kim, W. J. (1999). Lacrimal gland HGF, KGF, and EGF mRNA levels increase after corneal epithelial wounding. Investigative ophthalmology & visual science, 40 (10), 2185-21903 Bonini, S., Lambiase, A., Rama, P., Caprioglio, G., & Aloe, L. (2000). Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology, 107(7), 1347-1351. Investor Contact: Tim McCarthy LifeSci Advisors, LLC (212) 915-2564 investors@oysterpointrx.com Media Contact: Sheryl Seapy, Real Chemistry (213) 262-9390sseapy@realchemistry.com