The Lundquist Institute

An older form of hormone therapy taken to ease the symptoms of menopause could increase the risk of ovarian cancer, according to results released Thursday from two studies involving tens of thousands of women. Another hormonal regimen didnt seem to carry this same risk, researchers found.The results should help settle debate over the relative risk of cancer associated with estrogen- and progestin-based hormonal therapy. Still, researchers noted, the absolute risk of ovarian cancer associated with either regimen is low.Before these randomized, placebo-controlled clinical trials, observational studies examining the influence of estrogen plus progestin on ovarian and endometrial cancers gave mixed results, said Rowan Chlebowski, of the Lundquist Institute in California, in a statement on the findings. Our study provides the only long-term information from a randomized clinical trial on two common cancers in postmenopausal women for two of the most commonly used medications.Part of the Womens Health Initiative that began in 1991, the studies ran between 1993 and 1998 and enrolled more than 27,000 women aged 50 to 79 years from across the U.S. The findings, which stem from a 20-year follow-up analysis, will be presented at the American Society of Clinical Oncologys annual meeting, being held in Chicago from May 31 to June 4.For postmenopausal women, hormone therapy has long been used to help manage hot flashes and sleep disturbances. During the time of the studies, the standard option for women who had had a hysterectomy, or their uteruses removed, was conjugated equine estrogen, or CEE. Women who still had a uterus often received CEE plus medroxyprogesterone acetate, or MPA.The WHI studies randomized women without a uterus to either CEE or a placebo, and those who had a uterus to receive CEE plus MPA or a placebo.Results show that CEE was associated with a higher risk of developing ovarian cancer compared to placebo, with 35 cases in the hormone therapy group versus 17 in the placebo group. The risk of dying from ovarian cancer was almost three times higher with among CEE-treated women than in those given placebo.But among women with uteruses who took CEE plus MPA, there was no statistically significant increase in the risk of developing ovarian cancer, or in dying from it. Notably, women on this regimen had a 28% lower risk of developing uterine cancer, researchers found.While this new information is an important part of patient counseling and education, given the low numbers, it should not necessarily impact a woman's decision to take menopausal hormone therapy for symptomatic relief of menopausal symptoms, said Eleonora Teplinsky, a physician at Valley Mount Sinai Comprehensive Cancer Care, in a statement provided by ASCO.CEE was for years a common menopausal treatment. But its use declined following prior WHI findings on associated heart risks that led to Food and Drug Administration warnings.Hormonal therapy is not currently recommended for all postmenopausal women. Groups like the American Cancer Society have previously flagged ovarian cancer risk, while the FDA has highlighted the risk of endometrial cancer. The regulator advises women who do take hormonal therapy for menopausal symptoms to use the lowest dose for as short a time as possible.However, WHI researchers noted that ovarian cancer is not currently incorporated as a risk in prescribing guidelines for menopausal hormone therapy. They also suggested that their findings prompt reconsideration of advice around estrogen-only use in ovarian cancer survivors.Some drugmakers, meanwhile, are developing non-hormonal medications that could become an alternative to hormone therapy for treating vasomotor symptoms. '

In vivo data demonstrated response rate for oral SCY-247 similar to current standard of care, intravenous Liposomal Amphotericin B, for the treatment of mucormycosisCombination of SCY-247 and Liposomal Amphotericin B showed significant enhancement in survival and reduction in fungal burden in lung and brain tissue compared to monotherapies JERSEY CITY, N.J., Jan. 29, 2024 (GLOBE NEWSWIRE) -- SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug-resistant infections, today announced the presentation of preclinical efficacy data on its second generation fungerp candidate SCY-247. Dr. Ashraf Ibrahim, PhD, FAAM, FECCM, Professor of Medicine in the Division of Infectious Diseases at the David Geffen School of Medicine at UCLA and an investigator at the Lundquist Institute at Harbor-UCLA Medical Center, presented a poster entitled, “SCY-247, a novel second-generation IV/oral triterpenoid antifungal, is efficacious in the neutropenic mouse model of pulmonary mucormycosis,” at the 11th Advances Against Aspergillosis and Mucormycosis (AAAM) Conference in Milan, Italy from January 25 – 27. Mucormycosis is a life-threatening fungal infection with an associated mortality that ranges from 46% to 96%4, most commonly affecting immunocompromised patients including those with leukemia, patients undergoing bone marrow transplants, and patients affected by severe COVID or uncontrolled diabetes mellitus. In this highly lethal mouse model of mucormycosis, SCY-247 showed very promising in vivo efficacy. Orally administered SCY-247 resulted in 40% and 50% survival at 21 days post infection for the intermediate (32 mg/kg) and high doses (48 mg/kg), respectively, compared to 0% survival in the placebo group (p = 0.011 and 0.007, respectively). This is comparable to the 40% survival observed in the control group treated with 10 mg/kg of intravenous standard of care of liposomal amphotericin B (LAMB) (p = 0.008 vs. placebo). Even more encouraging was a 90% survival observed in the group receiving combination therapy of SCY-247 32 mg/kg plus LAMB 10 mg/kg (p < 0.0001 vs. placebo and p < 0.05 vs. monotherapy). The positive survival data correlated with a statistically significant fungal burden reduction in both lung and brain tissue with SCY-247 32 mg/kg dose (p = 0.0288 and 0.0355 vs. placebo, respectively) and 48 mg/kg dose (p = 0.0015 and 0.0052 vs. placebo, respectively) as well as with the active control LAMB (p = 0.0005 vs. placebo for both lung and brain tissues). The combination treatment of SCY-247 plus LAMB demonstrated the greatest reduction in fungal burden and was highly statistically significant in both lung and brain tissue (both p < 0.0001 vs. placebo). “The potent antifungal efficacy of SCY-247 in a murine model of pulmonary mucormycosis alone and in combination with liposomal amphotericin B provides an important preclinical rationale for further development of this new therapeutic agent,” said Thomas J. Walsh, MD, FCCP, FAAM, FIDSA, Director of the Center for Innovative Therapeutics and Diagnostics in Richmond, Virginia. “The opportunity to significantly improve the lives of patients suffering from life-threatening fungal infections is a key driver for all of us at SCYNEXIS, and positive results like the ones presented at AAAM reinvigorate our commitment to providing innovative tools in the fight against deadly infections,” said David Angulo, M.D., President and Chief Executive Officer of SCYNEXIS. “These positive data continue to accumulate and define the unique properties of SCY-247, highlighting its potential to be differentiated from currently available antifungals. We continue to expeditiously advance the development of this promising antifungal with plans to be in a clinical stage by year end.” The work reported here utilized the National Institute of Allergy and Infectious Diseases’ (NIAID’s) suite of preclinical services for in vivo testing (Contract No. HHSN272201700039I/ 75N93022F00001). About Mucormycosis Mucormycosis is an often life-threatening fungal infection that typically affects the nose, sinuses, eyes, and brain and is characterized by tissue necrosis and rapid progression.1 While multiple types of fungi can cause mucormycosis, R. delemar and R. oryae are the most common, accounting for ~70% of cases.2 Infections are most common in patients with compromised immune systems, including those with cancer, diabetes or those taking steroid medications.3 The overall mortality rate of mucormycosis ranges from 46% to 96%.4 About SCY-247 SCY-247 is a second-generation antifungal compound, from a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids (fungerps), under development as therapeutic options for systemic fungal diseases. The triterpenoid class of antifungals represents the first new class of antifungal compounds since 2001. These agents combine the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and intravenous (IV) formulations. SCY-247 is in pre-IND development stage and has demonstrated broad-spectrum antifungal activity, in vitro and in vivo. SCYNEXIS anticipates that the U.S. Food and Drug Administration (FDA) may grant SCY-247 Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of SCY-247. About SCYNEXIS SCYNEXIS, Inc. (NASDAQ: SCYX) is a biotechnology company pioneering innovative medicines to help millions of patients worldwide overcome and prevent difficult-to-treat infections that are becoming increasingly drug-resistant. SCYNEXIS is developing the company’s proprietary antifungal platform “fungerps”. Ibrexafungerp, the first representative of this novel class, has been licensed to GSK. The U.S. Food and Drug Administration (FDA) approved BREXAFEMME® (ibrexafungerp tablets) in June 2021, for its first indication in vulvovaginal candidiasis (VVC), followed by a second indication in November 2022, for reduction in the incidence of recurrent VVC. Late-stage clinical investigation of ibrexafungerp for the treatment of life-threatening invasive fungal infections in hospitalized patients is ongoing. Additional antifungal assets from this novel class are currently in pre-clinical and discovery phase, including the compound SCY-247. For more information, visit www.scynexis.com. Forward-Looking Statements Statements contained in this press release regarding expected future events or results are "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including but not limited to statements regarding: SCYNEXIS’s plans to begin a clinical study in SCY-247 by year end and SCY-247’s potential to be differentiated from currently available antifungals. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks inherent in regulatory and other costs in developing products. These and other risks are described more fully in SCYNEXIS' filings with the Securities and Exchange Commission, including without limitation, its most recent Annual Report on Form 10-K filed on March 31, 2023, including under the caption "Risk Factors." All forward-looking statements contained in this press release speak only as of the date on which they were made. SCYNEXIS undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. CONTACT: Investor RelationsIrina KofflerLifeSci AdvisorsTel: (646) 970-4681ikoffler@lifesciadvisors.com 1Hernández JL, Buckley CJ. Mucormycosis. [Updated 2023 Jun 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan https://pubmed.ncbi.nlm.nih.gov/31335084/ 2 Ribes JA, Vanover-Sams CL, Baker DJ. Zygomycetes in human disease. Clin Microbiol Rev. 2000 Apr;13(2):236-301. doi: 10.1128/CMR.13.2.236. PMID: 10756000; PMCID: PMC100153. https://pubmed.ncbi.nlm.nih.gov/10756000/ 3 Akshay R, Nguyen TH, Rising incidence of mucormycosis in patients with COVID-19: another challenge for India amidst the second wave? Lancet, 2021 June, https://doi.org/10.1016/S2213-2600(21)00265-4 4https://www.cdc.gov/fungal/diseases/mucormycosis/statistics.html

DOYLESTOWN, Pa., July 18, 2023 (GLOBE NEWSWIRE) -- Advent Therapeutics, Inc., a biotechnology company pioneering an optimized retinol palmitate (vitamin A) drug product as a breakthrough non-invasive inhaled neonatal lung therapy, has been awarded a $3 million National Institutes of Health (NIH) Small Business Innovation Research (SBIR) Phase IIB grant. This grant allows the Company to position its novel aerosolized vitamin A formulation for commercialization in 2025 to prevent Bronchopulmonary Dysplasia (BPD). BPD is a rare disease and the most common serious complication facing premature infants, resulting in significant morbidity and mortality. There are currently no approved therapies. With this grant, the Company has now received in excess of $6 million from NIH for its neonatal programs. “This NIH award will allow us to greatly accelerate the development and advance towards approval of our optimized vitamin A drug product,” commented David L. Lopez, Chief Executive Officer, Advent Therapeutics. “Advent’s novel, precisely optimized products are intended to address the unmet medical need of BPD facing premature infants and reduce morbidity and mortality in this fragile patient population. Our primary focus is to accelerate the path to commercialization, first in the US, then EU and worldwide. US launch of Advent’s initial vitamin A drug product for injection is possible in early 2025 with potential peak annual revenues in excess of $100 million for the prevention of BPD. In addition, we intend to pursue broader applications for our novel retinol palmitate drug product that have significant market potential.” This SBIR Phase IIB grant, awarded under the auspices of both the National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS), will support development of Advent’s proprietary aerosolized formulation of vitamin A. The $3 million provided under the SBIR Phase IIB grant will be used to complete preclinical requirements and manufacturing scale-up leading to pivotal human clinical trials with Advent’s inhalable retinol palmitate product to potentially gain US and other worldwide marketing approvals. Dr. Virender Rehan, Advent’s Principal Investigator at the Lundquist Institute, Professor of Pediatrics, David Geffen School of Medicine at UCLA, Chief of the Division of Neonatology, and Director of the Neonatal Intensive Care Unit, Harbor-UCLA Medical Center, said, “BPD is the most frequent serious complication that affects roughly 15,000 infants annually in the US, with an even greater number of premature infants at risk. With no approved drugs for BPD, these fragile, at-risk premature infants require prolonged mechanical ventilation or oxygen support and lengthy hospital stays often resulting in recurring hospitalizations and pulmonary infections. A baby with BPD adds significant emotional constraints for the family and financial burden to the healthcare system.” Advent has longstanding collaborations with Dr. Rehan and the world-renowned Lundquist Institute for Biomedical Innovation. The Lundquist Institute is one of the foremost independent, non-profit research institutes in the US and is partnered with Harbor-UCLA Medical Center. Dr. Virender continued, “I am extremely pleased to be involved in developing Advent’s novel form of inhalable vitamin A therapy. This product has the potential to be a “first-in-class” therapy capable of non-invasively delivering a safe and effective aerosolized vitamin A dose directly to the neonate’s lung. A lung-targeted inhalation therapy that could effectively reduce development of BPD would have significant clinical, financial, and societal implications by directly addressing co-morbidities suffered by these fragile patients.” Advent has previously been awarded Orphan Drug Designation in both US and Europe for its proprietary vitamin A formulation. Orphan Drug Designation provides incentives including assistance with drug development process and exemption from user fees, as well as a seven-year window of exclusive US marketing rights (10 years in Europe) following marketing approval. ABOUT BRONCHOPULMONARY DYSPLASIA (BPD) BPD is a rare disease and the most common serious complication facing premature infants, resulting in significant morbidity and mortality. It is an extremely costly respiratory disorder afflicting premature infants for which there is currently no approved drugs worldwide. Annually, in both US and Europe, there are approximately 100,000 premature infants at-risk for BPD and many more in Asia-Pacific, Latin America and throughout the world. Hospital costs in the US for treating a BPD infant in the first year are approximately $442,000 with an average first year hospital stay of 103 days. US healthcare costs of treating babies with BPD have been estimated as $2.4 billion per year. NOVEL VITAMIN A DRUG PRODUCT MANUFACTURING Advent is completing manufacturing scale-up of its proprietary optimized retinol palmitate drug product at Pace® Analytical Life Sciences. Commercial product for administration by injection is expected by 4Q 2024. Pace is a highly regarded contract development and manufacturing organization (CDMO) with facilities throughout the US, including San Diego, CA, where Advent’s manufacturing scale-up is being completed, and Salem, NH, where commercial batches will be produced. To support commercialization, Advent has also established a partnership with dsm-firmenich that provides Advent with a supply of highest quality active pharmaceutical ingredient (API) and access to dsm-firmenich’s Drug Master File for US and other worldwide regulatory authority marketing approvals. dsm-firmenich is one of the largest multinational companies that produces API and other products for the life sciences industry. ABOUT ADVENT THERAPEUTICS Advent Therapeutics, Inc. (Advent) was founded by senior industry executives with extensive expertise and proven track records in developing products in respiratory diseases for neonatal, pediatric and similar Orphan Drug “niche” markets and therapies. Advent is committed to developing life-changing medicines for the most-fragile preterm infants and is focusing on novel approaches to addressing serious unmet medical needs facing this significantly underserved Orphan Drug patient population. Advent has developed a proprietary formulation of optimized retinol palmitate (vitamin A) specifically designed for dosing to preterm infants to address vitamin A deficiency and associated serious complications of prematurity such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and neonatal sepsis, all significantly impacting both short- and long-term clinical outcomes. The Company is also pursuing the potential of inhaled optimized retinol palmitate to mitigate acute lung injury (ALI) and address CBRN (chemical, biological, and radio-nuclear) threat agents, and pulmonary infections (bacterial, influenza, SARS-CoV-2), which often progress to life-threatening acute respiratory distress syndrome (ARDS). These represent large therapeutic opportunities for which Advent expects to partner with others for development and commercialization. For more information, please visit Advent’s website at KEY PARTNERS AND SPONSORS dsm-firmenich – Advent has a supply arrangement with dsm-firmenich that provides the Company with supplies of vitamin A palmitate, the critical high-quality active pharmaceutical ingredient (API), necessary for development and commercialization. dsm-firmenich is a world leading supplier of vitamins, carotenoids and other nutritional solutions for the pharmaceutical industry. dsm-firmenich is a Swiss-Dutch company, listed on the Euronext Amsterdam, with operations in almost 60 countries and revenues of more than €12 billion. Through their collaboration since 2015, dsm-firmenich has provided invaluable technical support and maintains an active FDA Drug Master File (DMF) that will be incorporated into Advent’s US and other worldwide regulatory approvals. BEN FRANKLIN TECHNOLOGY PARTNERS OF SOUTHEASTERN PA – Advent received seed capital from Ben Franklin and maintains a strong relationship that offers business and technical expertise and the potential for additional venture funding. Ben Franklin has been ranked as a top 10 venture capital firm in Pitchbook and has invested over $200 million in more than 2,000 regional enterprises, many of which have gone on to become industry leaders. PENNSYLVANIA BIOTECHNOLOGY CENTER (BUCKS COUNTY) – Advent maintains lab and office space at the Pennsylvania Biotechnology Center located in Doylestown, Bucks County. The PABC is one of the nation’s leading biotech incubators and seeks to advance biotechnology in the region and foster the launch of new ideas and discoveries that will make a difference. FORWARD LOOKING STATEMENTS This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. The inclusion of forward-looking statements should not be regarded as a representation by us that any of our plans will be achieved. Any or all of the forward-looking statements in this press release may turn out to be wrong and can be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. For example, with respect to statements regarding the goals, progress, timing, and outcomes of discussions with regulatory authorities, actual results may differ materially from those set forth in this release due to the risks and uncertainties inherent in our business. All forward-looking statements are qualified in their entirety by this cautionary statement, and we undertake no obligation to revise or update this news release to reflect events or circumstances after the date hereof. Media and investor contact: David L. Lopez david.lopez@advent-therapeutics.com