Eleven Therapeutics Ltd.

MIAMI, FL, May 14, 2024 (GLOBE NEWSWIRE) -- Veru Inc. (NASDAQ: VERU), a late clinical stage biopharmaceutical company focused on developing innovative medicines for preserving muscle for high quality weight loss, oncology, and viral induced acute respiratory distress syndrome, today announced that Mitchell Steiner, M.D., Chairman, President, and Chief Executive Officer, will be a Keynote Speaker at Biomed Israel 2024: The 22nd National Life Science & Technology Week, taking place May 21-23, 2024, in Tel Aviv, Israel. The keynote presentation will highlight the concerns that (i) muscle loss caused by GLP-1 receptor agonists may be partly responsible for weight loss plateau, (ii) upon stopping GLP-1 RA, the fat and weight rebound regain, and (iii) such muscle loss may accelerate the development of frailty in at-risk older sarcopenic obese patients who are at risk for physical function limitations. The presentation will take place on Wednesday, May 22, 2024, from 2:30 PM – 4:30 PM Israel Daylight Time. Keynote Title: Make GLP-1 weight loss drugs more effective and precise -- get greater fat loss by preserving muscle mass and function? Moderators: Dr. Boaz Hirshberg, MD, Senior Vice President, Clinical Sciences General Medicine, Regeneron Pharmaceuticals and Iris Grossman, PhD, CThO, Eleven TherapeuticsPresentation Date: Wednesday, May 22, 2024Presentation Time: 2:30 PM – 4:30 PM Israel Daylight TimePresentation Location: Hall B Additional information on the meeting can be found on the Biomed Israel 2024 website: https://kenes-exhibitions.com/biomed/ About the Enobosarm Phase 2b clinical trialThe Phase 2b, multicenter, double-blind, placebo-controlled, randomized, dose-finding clinical trial is designed to evaluate the safety and efficacy of enobosarm 3mg, enobosarm 6mg, or placebo as a treatment to preserve muscle and augment fat loss in approximately 90 patients with sarcopenic obesity or overweight elderly (>60 years of age) patients receiving semaglutide (Wegovy®). The primary endpoint is difference in total lean body mass, and the key secondary endpoints are differences in total body fat mass and physical function as measured by stair climb test at 16 weeks. The Phase 2b clinical trial is actively enrolling patients from up to 15 clinical sites in the United States. Topline clinical results from the trial are expected by the end of calendar year 2024. After completing the efficacy dose-finding portion of the Phase 2b clinical trial, it is expected that participants will then continue in blinded fashion into a Phase 2b extension clinical trial where all patients will stop receiving a GLP-1 RA, but will continue taking placebo, enobosarm 3mg, or enobosarm 6mg for an additional 12 weeks. The Phase 2b extension clinical trial will evaluate whether enobosarm can maintain muscle and prevent the fat and weight gain that occurs after discontinuing a GLP-1 RA. The topline results of the separate blinded Phase 2b extension clinical study are expected in calendar Q2 2025. About Sarcopenic ObesityAccording to the CDC, 41.5% of older adults have obesity in the United States and could benefit from a weight loss medication. Up to 34.4% of these obese patients over the age of 60 have sarcopenic obesity. This large subpopulation of sarcopenic obese patients is especially at risk for taking GLP-1 drugs for weight loss as they already have critically low amount of muscle due to age-related muscle loss. Further loss of muscle mass when taking a GLP-1 RA medication may lead to muscle weakness leading to poor balance, decreased gait speed, mobility disability, loss of independence, falls, bone fractures and increased mortality which is a condition like age-related frailty. Because of the magnitude and speed of muscle loss while on GLP-1 RA therapy for weight loss, GLP-1 RA drugs may accelerate the development of frailty in older obese or overweight elderly patients. About EnobosarmEnobosarm (aka ostarine, MK-2866, GTx-024, and VERU-024), a novel oral daily selective androgen receptor modulator (SARM), has been previously studied in 5 clinical studies involving 968 older normal men and postmenopausal women as well as older patients who have muscle wasting because of advanced cancer. Advanced cancer simulates a “starvation state” where there is significant unintentional loss or wasting of both muscle and fat mass which is similar to what is observed with in patients taking GLP-1 RA drugs. We believe the totality of the clinical data from these previous five clinical trials demonstrates that enobosarm treatment leads to dose-dependent increases in muscle mass with improvements in physical function as well as significant dose-dependent reductions in fat mass. The patient data that were generated from these five enobosarm clinical trials in both elderly patients and in patients with a cancer induced starvation-like state provide strong clinical rationale for enobosarm. The expectation is that enobosarm in combination with a GLP-1 RA would potentially augment the fat reduction and total weight loss while preserving muscle mass. Importantly, enobosarm has a large safety database, which includes 27 clinical trials involving 1581 men and women, some of which included patients dosed for up to 3 years. In this large safety database, enobosarm was generally well tolerated with no increases in gastrointestinal side effects. This is important as there are already significant and frequent gastrointestinal side effects with a GLP-1 RA treatment alone. About Veru Inc.Veru is a late clinical stage biopharmaceutical company focused on developing novel medicines for the treatment of metabolic diseases, oncology, and ARDS. The Company’s drug development program includes two late-stage novel small molecules, enobosarm and sabizabulin. Enobosarm, a selective androgen receptor modulator (SARM), is being developed for two indications: (i) Phase 2b clinical study of enobosarm as a treatment to augment fat loss and to prevent muscle loss in sarcopenic obese or overweight elderly patients receiving a GLP-1 RA who are at-risk for developing muscle atrophy and muscle weakness and (ii) subject to the availability of sufficient funding, Phase 3 ENABLAR-2 clinical trial of enobosarm and abemaciclib for the treatment of androgen receptor positive (AR+), estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer in the 2nd line setting. Sabizabulin, a microtubule disruptor, is being developed as a Phase 3 clinical trial for the treatment of hospitalized patients with viral-induced ARDS. The Company does not intend to undertake further development of sabizabulin for the treatment of viral-induced ARDS until we obtain funding from government grants, pharmaceutical company partnerships, or other similar third-party external sources. The Company also has an FDA-approved commercial product, the FC2 Female Condom® (Internal Condom), for the dual protection against unplanned pregnancy and sexually transmitted infections. Forward-Looking StatementsThis press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, express or implied statements related to whether and when the phase 2b trial of enobosarm discussed above will produce topline data or patients will progress into the extension study, the planned design, number of sites, timing, endpoints, patient population and patient size of such trial and whether such trial will successfully meet any of its endpoints, whether enobosarm will enhance weight loss or preserve muscle in, or meet any unmet need for, obesity patients and whether it will enhance weight loss, whether the Company’s scientific advisors will make valuable contributions to the Company’s enobosarm program and whether the Company will be successful in its transformation into a late stage biopharmaceutical company focused on obesity and oncology. The words "anticipate," "believe," "could," "expect," "intend," "may," "opportunity," "plan," "predict," "potential," "estimate," "should," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based upon current plans and strategies of the Company and reflect the Company's current assessment of the risks and uncertainties related to its business and are made as of the date of this press release. The Company assumes no obligation to update any forward- looking statements contained in this press release because of new information or future events, developments or circumstances. Such forward-looking statements are subject to known and unknown risks, uncertainties and assumptions, and if any such risks or uncertainties materialize or if any of the assumptions prove incorrect, our actual results could differ materially from those expressed or implied by such statements. Factors that may cause actual results to differ materially from those contemplated by such forward-looking statements include, but are not limited to: the development of the Company’s product portfolio and the results of clinical studies possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical studies and the ability to enroll subjects in accordance with planned schedules; the ability to fund planned clinical development as well as other operations of the Company; the timing of any submission to the FDA or any other regulatory authority and any determinations made by the FDA or any other regulatory authority; the Company’s existing product, FC2, and any future products, if approved, possibly not being commercially successful; the ability of the Company to obtain sufficient financing on acceptable terms when needed to fund development and operations; demand for, market acceptance of, and competition against any of the Company’s products or product candidates; new or existing competitors with greater resources and capabilities and new competitive product approvals and/or introductions; changes in regulatory practices or policies or government-driven healthcare reform efforts, including pricing pressures and insurance coverage and reimbursement changes; risks relating to the Company's development of its own dedicated direct to patient telehealth platform, including the Company's lack of experience in developing such a platform, potential regulatory complexity, development costs, and market awareness and acceptance of any telehealth platform we develop; risks relating to our ability to increase sales of FC2 after significant declines in recent periods due to telehealth industry consolidation and the bankruptcy of a large telehealth customer; the Company’s ability to protect and enforce its intellectual property; the potential that delays in orders or shipments under government tenders or the Company’s U.S. prescription business could cause significant quarter-to-quarter variations in the Company’s operating results and adversely affect its net revenues and gross profit; the Company’s reliance on its international partners and on the level of spending by country governments, global donors and other public health organizations in the global public sector; the concentration of accounts receivable with our largest customers and the collection of those receivables; the Company’s production capacity, efficiency and supply constraints and interruptions, including potential disruption of production at the Company’s and third party manufacturing facilities and/or of the Company’s ability to timely supply product due to labor unrest or strikes, labor shortages, raw material shortages, physical damage to the Company’s and third party facilities, product testing, transportation delays or regulatory actions; costs and other effects of litigation, including product liability claims and securities litigation; the Company’s ability to identify, successfully negotiate and complete suitable acquisitions or other strategic initiatives; the Company’s ability to successfully integrate acquired businesses, technologies or products; and other risks detailed from time to time in the Company’s press releases, shareholder communications and Securities and Exchange Commission filings, including the Company's Form 10-K for the year ended September 30, 2023, as amended by the Form 10-K/A, and subsequent quarterly reports on Form 10-Q. These documents are available on the “SEC Filings” section of our website at www.verupharma.com/investors. * Wegovy® is a registered trademark of Novo Nordisk A/S Investor and Media Contact:Samuel FischExecutive Director, Investor Relations and Corporate CommunicationsEmail: veruinvestor@verupharma.com

Cardiovascular is one of the areas Novo Nordisk plans to establish its presence by 2025, as per the company’s Q4 2023 quarterly report. Image Credit: Maurice NORBERT / Shutterstock. Novo Nordisk has agreed to acquire Germany-based Cardior Pharmaceuticals for up to €1bn ($1.1bn) to expand its cardiovascular pipeline. The deal is expected to close in Q2 2024. Cardior’s lead candidate is a Phase II heart failure candidate, CDR132L. The therapy is an antisense oligonucleotide, which selectively blocks abnormal levels of the microRNA molecule, miR-132. miR-132 plays a part in cardiac processes, as it is overexpressed in patients with heart failure. CDR132L is being evaluated in a placebo-controlled Phase II trial (NCT05350969) in 280 patients with left-sided heart failure following myocardial infarction. The trial is expected to conclude in March 2025, as per ClinicalTrial.Gov . Novo plans to expand CDR132L’s indication and investigate the therapy in a Phase II trial in chronic heart failure patients with cardiac hypertrophy. Novo has had recent success in cardiovascular indication with its blockbuster weight loss therapy, Wegovy (semaglutide). Earlier this month, the US Food and Drug Administration (FDA) approved Wegovy to reduce the risk of cardiovascular death , heart attack and stroke in obese or overweight adults with cardiovascular disease. The company has invested in expanding its cardiovascular portfolio through multiple deals in recent months. Last month, Novo signed a $1.46bn deal with US-based biotech Neomorph to discover and develop multiple ‘molecular glue’ protein degraders for cardiometabolic disorders and rare diseases. According to the agreement, Neomorph will be responsible for the discovery and preclinical research while Novo will have exclusive rights to further clinical development and commercialisation. See Also: Ingersoll Rand to expand life science presence with $2.3bn ILC buyout Esperion snags US label expansion for cardiovascular disease drugs In July 2023, Novo signed a research partnership with Eleven Therapeutics to identify novel nucleic acid molecules to treat cardiometabolic diseases by leveraging the latter’s DELiveri platform. DELiveri uses DNA-encoded libraries (DELs), along with machine learning and AI technologies to identify conjugates that can transport therapeutic molecules. Apart from the investment in diabetes and weight loss , Novo also plans to establish its presence in emerging disease areas, such as metabolic dysfunction-associated steatohepatitis (MASH) and chronic kidney disease. Last month, the Danish pharmaceutical partnered with Cellarity to discover and develop therapies for MASH.

Pictured: A collage of medical notes and anatomy/Nicole Bean for BioSpace With all the recent headlines being made in genetic medicine, a presentation from Turn Biotechnologies announcing the first successful in vivo delivery of messenger RNA to the skin with no off-target effects flew largely under the radar. While Turn Bio will still need to prove its platform in the clinic, the news may mark another step toward surmounting the hurdles the industry has faced with delivering RNA therapeutics outside of the liver. The potential for RNA-based medicines is great. As current small molecule and antibody drugs target only around 0.05% of the human genome, RNA therapeutics—including antisense oligonucleotides (ASOs), small interfering RNA interference (siRNA) and mRNA therapeutics—could significantly broaden the range of druggable targets, if they can safely and accurately reach their destinations. The discovery a decade ago that the conjugation of GalNac, an amino sugar moiety, to siRNA and ASO drugs could efficiently target the liver was a significant breakthrough for RNA therapeutics. Alnylam’s Amvuttra (vutrisiran), for polyneuropathy of hereditary ATTR (hATTR) amyloidosis, makes use of GalNac delivery, as does Novartis’ Leqvio (inclisiran), which reduces bad cholesterol. The problem, Iris Grossman, chief therapeutics officer at Eleven Therapeutics, told BioSpace last year, is that very few similar mechanisms have been discovered. Endosomal Escape and Targeting Steven Dowdy, a professor of cellular and molecular medicine at the University of California, San Diego, placed the challenges to extrahepatic delivery into two categories. For mRNA therapeutics, the biggest obstacles are specific targeting and immunogenicity, Dowdy told BioSpace. For RNA conjugates like ASOs and siRNAs, he said, the main challenge is endosomal escape. Steven Dowdy RNA therapeutics are taken up into the cell by endocytosis, but 99% or more of them are entrapped in an acidified endosome and degraded. The human body has developed natural defenses against RNA-based viruses, making the immune system resistant to foreign RNA. “Our therapeutics look to the body, to cells, like invading RNA,” Dowdy said. Most drug developers ensconce mRNAs in a lipid nanoparticle (LNP), which acts as both a protective shield and an endosomal escape device and allows around 5% of the therapy to make it unscathed into cells. Small RNA therapeutics lack such an endosomal escape device, so only 0.3% to 1% of the conjugate escapes the endosome into the target cell. In mRNA delivery, Dowdy said, targeting is the rate limiting step. While the APOE protein binds efficiently to the surface of certain LNPs, carrying them to the liver, he said similarly targeted proteins that enable the RNA to reach, say, the pancreas or cardiac myocytes, don’t exist. While chemists are trying to synthesize different types of lipids to bind proteins that would carry the LNP to other cell types, Dowdy said this has proven a difficult problem to solve for highly specific targeting. The Largest Organ For Anja Krammer, CEO of Turn Bio, the first objective is to effectively deliver the RNA to the cell itself. To solve this challenge, the company is creating tuneable RNA, which involves precisely delivering cargo to the cell and controlling the expression of the genetic information it carries. “Cells throughout the body and in different tissue types have very different responses and require a different level of delivery,” Krammer told BioSpace. Turn Bio’s pipeline includes investigational therapies for skin wounds, cellular exhaustion and frailty. Anja Krammer The second component, she said, is the vehicle that carries the RNA into a specific tissue type. Turn Bio found that carriers used for mRNA vaccine delivery were not effective or efficient enough for therapeutic delivery, so the company developed a proprietary LNP system with its own ionizable lipid. With vaccines, “you need just a very small amount of reaction in the body to be able to trigger that immune response,” Krammer said. But with a large organ like the skin, “you need to be able to hit a lot of cells, need to be able to transfect a lot of cells, and chances are, you’re gonna need to do it more than once.” Current tissue delivery systems create a lot of immunogenicity due to the PEG lipids used to keep them stable, she added. Turn Bio’s proprietary approach uses a stabilization system with a controlled release specific to a particular tissue environment. The preclinical data reported in November showed that “we now can contain that delivery within the skin tissue without the uptake into organs” such as the liver and spleen, Krammer said. The company plans to submit an Investigational New Drug application by the end of 2024. The Central Nervous System RNAi therapies like Alnylam’s Amvuttra and Onpattro (patisiran)—which both target the liver—work by silencing particular genes that cause or contribute to disease. They do so by degrading the genes’ mRNA. Vasant Jadhav Alnylam’s medicines leverage one of two platforms. In the first, siRNA is encapsulated within an LNP and delivered via IV infusion. Onpattro, the company’s first approved drug, for polyneuropathy of hATTR amyloidosis, is delivered in this way. In the second, a modified siRNA is conjugated to a targeting ligand to help it locate a specific cell or tissue within the body. The modifications provide stability against nucleases that would otherwise degrade the siRNA and also help minimize immune recognition of the siRNA, said Alnylam Chief Technology Officer Vasant Jadhav. Alnylam uses two conjugate systems: GalNAc conjugates and central nervous system (CNS)-targeted siRNA conjugates. Having proven its platforms with Onpattro and Amvuttra, Alnylam is turning its attention to the central nervous system. “RNAi is not limited to [the] liver,” Jadhav told BioSpace. “RNAi is a naturally occurring mechanism that’s happening in all cells and tissue types.” Some of these are in the CNS, where he said there are many genetically validated targets. Based on the delivery advances of the past 20 years, “we have highly modified siRNAs that have a targeting or delivery ligand that allows [the therapeutic] to be taken up in CNS,” Jadhav said. In October, Alnylam announced that its Alzheimer’s disease candidate, ALN-APP, showed sustained pharmacodynamic activity up to 10 months after administration in a Phase I trial. The treatment also led to “marked reductions” in two amyloid fragments implicated in Alzheimer’s and cerebral amyloid angiopathy, according to the company press release. “We’re really pleased with what we’re seeing in terms of the conjugates going from liver to now achieving this human [proof of concept] with the CNS molecules,” Jadhav said. The Lungs Clinical progress is also being made in delivering RNA to the lung. Jerusalem-based SpliSense is targeting a cystic fibrosis mutation with its ASO, SPL84. A short, vector-less single strand of RNA delivered directly to the lung via inhalation, SPL84 is designed to restore the function of the CFTR protein. In a recently completed Phase I study, it was shown to be safe and well tolerated in 32 healthy male volunteers. A Phase II trial, which will test the ASO in 18 cystic fibrosis patients carrying the 3849+10 kb C->T mutation, is slated to begin in the first half of next year. In a recently published preclinical study, SpliSense demonstrated the potential superiority of its inhaled approach to standard-size LNPs. In the study, which tested SPL84 in mouse and monkey lungs, the authors wrote that the candidate diffuses more effectively than these LNPs, primarily due to its small size. In comparison to Vertex and Moderna, whose CF program, VX-522, uses a LNP for delivery, SpliSense CEO Gili Hart said her company’s approach is “one hundred times more effective in relation to migration in the lungs.” In an interview last year, Ashley Mahoney, director of external communications at Vertex, told BioSpace that the company had successfully identified an LNP that can deliver the CFTR mRNA to target cells at levels that result in CFTR function levels associated with clinical benefit. While he declined to hazard a guess as to the next organ to see successful RNA delivery, Dowdy said: “If and when we solve the endosomal escape problem in a safe manner, that will open up the ability of RNA therapeutics to selectively treat . . . cancer, COVID and a multitude of other diseases.” Heather McKenzie is a senior editor at BioSpace. You can reach her at heather.mckenzie@biospace.com. Follow her on LinkedIn.