Facial Paralysis

TP-05 demonstrated tolerability and statistically significant tick mortality, suggesting potential for on-demand Lyme disease prophylaxisIRVINE, Calif., Feb. 22, 2024 (GLOBE NEWSWIRE) -- Tarsus Pharmaceuticals, Inc. (NASDAQ: TARS), whose mission is to focus on unmet needs and apply proven science and new technology to revolutionize treatment for patients, starting with eye care, today announced positive topline results from the Phase 2a Carpo trial evaluating TP-05 (lotilaner), a novel, investigational oral therapeutic for the prevention of Lyme disease. In this randomized, double-blind, placebo-controlled trial, the ability of TP-05 to kill ticks attached to subjects with a single treatment of TP-05 (low or high dose) was evaluated compared to placebo. Sterile, non-pathogenic nymphal ticks were placed on the skin of healthy human volunteers at two separate instances (one day prior to dosing and on Day 30 after dosing). Tick mortality was evaluated within 24 hours of attachment after each placement. In most cases, ticks must be attached for 36-48 hours or more before Lyme disease can be transmitted, so killing ticks within 24 hours of attachment can greatly increase the probability of disease prevention 1. Both the high and low doses of TP-05 demonstrated a statistically significant benefit in killing ticks compared to placebo. Specifically, after the Day 1 tick challenge, mean tick mortality was 97.0% (± 1.4 standard error, SE) and 92.0% (± 6.3 SE) for the high and low doses of TP-05, respectively, compared to only 5.0% (± 2.5 SE) for placebo (p < 0.0001). Similarly, at the 30-day challenge, mean tick mortality at 24 hours after placement was 89.0% (± 11.1 SE) and 91.0% (± 6.1 SE) for the high and low doses of TP-05, respectively, compared to only 9.0% (± 8.0 SE) for placebo (p<0.001). No statistically significant differences in tick mortality were observed between the two TP-05 treatment arms, and TP-05 was generally well tolerated. “Lyme disease remains a growing public health concern associated with long-term consequences for millions of patients and an estimated $1 billion dollar price tag for the U.S. healthcare system,” said Bobby Azamian, M.D., Ph.D., Chief Executive Officer and Chairman of Tarsus. “We are highly encouraged by these early proof-of-concept data and the opportunity to bring forward a novel, on-demand, oral treatment that addresses the root cause of disease – the ticks that transmit the bacteria that cause Lyme disease.” “The risk of infection from tick-borne diseases, such as Lyme disease and other serious infections, is growing at an alarming rate, and the consequences can be debilitating and long-lasting,” said Linden Hu, M.D., the Paul and Elaine Chervinsky Professor in Immunology at Tufts University School of Medicine and Principal Investigator for the Carpo trial. “The tick-kill rates seen at Day 1 and Day 30 suggest that TP-05 may have the potential to provide both rapid and durable protection against multiple tick-borne diseases, which would be a welcome alternative to vaccines in the prevention armamentarium.” About TP-05TP-05 is an oral systemic formulation of lotilaner, a well-characterized anti-parasitic agent that selectively inhibits parasite-specific GABA-Cl channels. TP-05 is believed to be the only non-vaccine, drug-based, preventative therapeutic in development designed to kill ticks to potentially prevent Lyme disease transmission. About Lyme DiseaseLyme disease is the most common vector-borne disease in the United States, transmitted to humans by Borrelia burgdorferi infection following the bite of a tick vector. Over 30 million Americans are considered to be at high or moderate risk of contracting Lyme disease, and there are approximately 300,000 – 400,000 cases in the U.S. each year. Lyme disease can potentially cause severe, often debilitating symptoms with permanent and irreversible damage. The disease can result in inflammation, nerve, joint and muscle pain and swelling, numbness, shortness of breath and – in severe cases – neurological complications such as facial palsy, vision issues and meningitis, including severe headaches and neck stiffness, as well as cardiac complications. Lyme disease can often go undetected and untreated because the ticks are not always noticed before they transmit the disease. People who spend extended amounts of time outdoors in wooded, grassy areas are at higher risk of Lyme disease. Data from the Centers for Disease Control and Prevention (CDC) show that the risk of Lyme disease is spreading to new geographical areas, resulting in a significant need for prophylactic solutions. Currently, there are no FDA-approved pharmacological prophylactic options for Lyme disease. About Tarsus Pharmaceuticals, Inc.Tarsus Pharmaceuticals, Inc. applies proven science and new technology to revolutionize treatment for patients, starting with eye care. Tarsus is advancing its pipeline to address several diseases with high unmet need across a range of therapeutic categories, including eye care, dermatology and infectious disease prevention. XDEMVY® (lotilaner ophthalmic solution) 0.25% is FDA approved in the United States for the treatment of Demodex blepharitis. Tarsus is also developing TP-03 as an investigational therapy for the treatment of Meibomian Gland Disease, TP-04 for the treatment of rosacea and TP-05 as an oral tablet for the prevention of Lyme disease, all of which are in Phase 2. Forward-Looking Statements Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements.” These statements include statements regarding the potential market size for TP-05 with respect to Lyme disease prevention, anticipated benefits of its product candidates including TP-05 and its potential applicability to Lyme disease prevention, as well as that of a variety of tick-borne diseases, the timing, objectives, and results of the clinical trials including the complete clinical results of the Carpo trial, anticipated regulatory and development milestones, our ability to continue investing in our business, and the quotations of Tarsus’ management and consultants. The words, without limitation, “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” or “would,” 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 or similar identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Further, there are other risks and uncertainties that could cause actual results to differ from those set forth in the forward-looking statement and they are detailed from time to time in the reports Tarsus files with the Securities and Exchange Commission, including Tarsus’ Form 10-K for the year ended December 31, 2022 filed on March 17, 2023, the Form 10-Q for the quarter ended September 30, 2023 filed on November 9, 2023 with the SEC, which Tarsus incorporates by reference into this press release, copies of which are posted on its website and are available from Tarsus without charge. However, new risk factors and uncertainties may emerge from time to time, and it is not possible to predict all risk factors and uncertainties. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. Any forward-looking statements contained in this press release are based on the current expectations of Tarsus’ management team and speak only as of the date hereof, and Tarsus specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Reference:1 Centers for Disease Control and Prevention, Lyme Disease Transmission. Media Contact: Adrienne Kemp Sr. Director, Corporate Communications (949) 922-0801 akemp@tarsusrx.com Investor Contact: David Nakasone Head of Investor Relations (949) 620-3223 DNakasone@tarsusrx.com

New AI app for facial palsy screening Computer scientists from Australia and Iraq have developed an AI-based diagnostic tool to detect facial palsy. They have come up with a detection system for facial palsy featuring a microcomputer, digital camera, and deep learning algorithm. Based on an entry in the journal BioMedInformatics, researchers from the Middle Technical University in Baghdad and the University of South Australia have trained computer vision systems using a dataset of 26,000 images to recognise the condition. Their algorithm was able to detect facial palsy in 20 participating patients with 98% accuracy. Besides identifying facial palsy, the researchers noted that the algorithm can also potentially help prevent misdiagnosis, which occurs in up to 20% of cases. Ear health app for Aboriginal children gets $1M Developers of a mobile app that helps raise awareness of ear health and mental wellbeing of Aboriginal children have received nearly A$1.5 million ($1 million) in grant funding from the Western Australia government. The SoundSmiles app is a project by researchers from Monash University, together with Curtin University and Ear Science Institute Australia. It engages children and students in activities related to their ears and wellbeing, as well as helps increase their digital literacy skills. The grant funding will support the second phase of the project, including its delivery to Pilbara and South-West communities that codesigned the app. HeraMED announces integration into MedicalDirector Clinical HeraMED has partnered with Telstra Health to integrate its remote pregnancy solution into its GP management platform. According to a media release, they intend to integrate HeraCARE into the MedicalDirector Clinical software, which Telstra Health now operates after purchasing MedicalDirector last year. The integration allows Telstra Health's primary care clients to provide prenatal healthcare through remote pregnancy monitoring.

The FAERS study of BCMA CAR-T and bispecific therapies comes as the FDA recently launched an investigation into potentially serious risks of developing secondary cancer after treatment with existing CAR-Ts BCMA-targeted therapies are transforming care for multiple myeloma patients. But these immunotherapies also come with various potentially dangerous side effects. A new study now looks at those risks from the FDA Adverse Event Reporting System (FAERS), hoping to help inform doctors in their treatment decisions. After going through about 4,400 reported adverse reactions for three FDA-approved BCMA agents from the 2019 to the second quarter of 2023, researchers found that Bristol Myers Squibb’s CAR-T therapy Abecma had the highest proportion of cytokine release syndrome (CRS) in its total reported events and that Johnson & Johnson and Legend Biotech’s CAR-T Carvykti reported the most Parkinson’s-like cases, whereas J&J’s bispecific antibody Tecvayli had a “notably higher” rate of infections. Because these three therapies are all approved for late-line treatment of myeloma, “clinicians will need to carefully consider their distinct toxicity profiles when choosing and sequencing treatments,” the study’s authors said in an abstract for the 65th American Society of Hematology annual meeting. Before getting into the details, it’s necessary to name a couple important limitations of the study. First, the rates calculated in the study only reflect how a specific type of side effect contributes to a drug’s overall adverse events. It’s different from the rate describing the frequency of an adverse event among all treated patients. Second, FAERS is a voluntary reporting system that doesn’t capture all adverse events happening in the real world. And the cases reported are not validated.  The nature of FAERS “makes it very tricky to really understand what’s happening” with these therapies, Rahul Banerjee, M.D., a multiple myeloma expert at the Fred Hutch Cancer Center who’s not involved in the study, said in an interview with Fierce Pharma.  “FAERS is helpful for rare, rare side effects,” Banerjee said. As for other more common problems such as CRS, which has become “bread-and-butter CAR-T management,” he wouldn’t draw too many conclusions from FAERS. As David Miklos, M.D., Ph.D., who leads the Blood and Bone Marrow Transplantation and Cellular Therapy program at Stanford University noted during a Q&A after the data presentation, there may be a more authoritative resource for recording adverse events from the CAR-Ts. The Center for International Blood & Marrow Transplant Research collects information from the FDA-mandated drug safety programs known as Risk Evaluation and Mitigation Strategy (REMS) for the CAR-Ts, he pointed out. Because of their risky safety profile, all commercial CAR-Ts are only offered through REMS in the U.S. Common problems Of all the adverse events, 874 were associated with Carvykti, 2,132 with Abecma and 1,363 with Tecvayli. The drugs got their FDA approvals in February 2022, March 2021 and October 2022, respectively. When it comes to CRS, a well-understood toxicity that’s spelled out in black-box warnings of all three drugs’ labels, Abecma had 344 reports (16.1% of all the drug’s adverse cases). CRS accounted for 10.3% of all adverse reports for Carvykti. Tecvayli had CRS making up 9.5% of its cases. For both CAR-Ts, CRS was the most common reason for deaths that weren’t caused by cancer relapse, followed by immune effector cell-associated neurotoxicity syndrome (ICANS), another known problem of CAR-T therapy. In the FAERS study, Carvykti had the lowest proportion of non-relapse deaths. For Tecvayli, COVID-19, sepsis and pneumonia—which are all infection-related complications—had the most frequent non-relapse deaths. Infections in general appeared to be a bigger problem among Tecvayli takers, as the proportion of infectious events in the J&J bispecific’s total reports was four times that of the two CAR-Ts combined. https://public.flourish.studio/visualisation/16079363/ But Banerjee said he would want to see a time-variant analysis to show how these adverse events evolve over time. For example, he pointed out an increasing use of intravenous immunoglobulin (IVIG) to control infections. “I do think as a field, as we get more familiar with these drugs, we’re learning more and more about how to prevent these side effects,” Banerjee said. Managing side effects Of the three BCMA therapies included in the study, Carvykti has shown the best efficacy. But some doctors flagged Parkinsonism as a concern that they’re closely monitoring for the J&J/Legend product. In this study, researchers found seven cases of Parkinsonism from Carvykti and four from Abecma. Plus, unexpected facial paralysis—a neurological disorder called Bell’s palsy—was reported almost exclusively from Carvykti, with 13 cases, versus none for Abecma and one for Tecvayli.  Since the Parkinson’s-like problem emerged, J&J and Legend have identified certain risk factors and developed a mitigation strategy that’s now being deployed in Carvykti’s clinical trials and commercial launch, Legend CEO Ying Huang, Ph.D., said in an interview with Fierce Pharma.  If a patient has a very high tumor burden at baseline, that could correlate to fast and high peak expansion of the CAR-T cells, which corresponds to this delayed neurotoxicity, Huang explained. To solve that problem, J&J and Legend suggest doctors first treat patients with bridging therapy to reduce that tumor burden. In addition, higher grade of CRS also appeared to correspond to Parkinsonism, according to Huang. So, doctors are advised to proactively treat CRS to prevent it from worsening. Besides, doctors could do a test as simple as a handwriting assessment to look for early signs of neurotoxicity. When discovered early, these neurotoxicities typically resolve after a standard four-week course of oral corticosteroid, Huang said. Overall, non-ICANS neurotoxicity was reported most often in Abecma’s adverse events reports at 10.1%. This group of events accounted for 6.4% of Carvykti’s adverse events. Both Carvykti and Abecma are under FDA review to potentially expand into earlier lines of treatment. But BMS said the agency plans to hold an advisory committee meeting to discuss Abecma’s KarMMa-3 trial with a focus on overall survival data, raising suspicions that the drug’s life extension benefit might be markedly worse than the 51% tumor progression improvement. Investigators will share the overall survival data at ASH on Monday. Discrepancies between overall survival and progression-free survival could largely be explained by non-relapse deaths. Again, Banerjee argued that non-relapse mortality should be examined together with the timing of the event and in the context of efficacy. FDA’s secondary cancer investigation The FAERS study presentation didn’t include any information on secondary cancer. But it comes as the FDA recently launched an investigation into potentially serious risks of developing secondary cancer after treatment with existing CAR-Ts, including four CD19-directed lymphoma products.  Almost simultaneously, an article published in ASH’s journal Blood described a 51-year-old male patient in Carvykti’s CARTITUDE-4 trial who developed CAR-positive T-cell lymphoma after Carvykti treatment. Legend’s Huang stressed that the FDA didn’t say anything about a causal link between CAR-T and secondary cancer. He also pointed to an up to 0.5% background incidence rate of T-cell lymphoma among multiple myeloma patients, as well as other treatments that a patient would typically go through that are also associated with an increased risk of secondary cancer. The FDA has identified 19 total T cell lymphoma cases from FAERS and clincal trials. Based on the tens of thousands of patients that have been treated, Huang argued “there’s overwhelming positive benefit-risk here.” Banerjee also argued that CAR-Ts’ benefits are “very real” against the risk of theoretical cancer, especially in heavily pretreated patients. Even if all those 19 cases were directly related to insertion mutations caused by CAR-Ts’ viral vectors, the benefit-risk calculation is still favorable, he said. Besides, Banerjee said he wouldn’t be surprised to one day see CAR-T recipients have a higher lifetime incidence of certain cancers versus non-recipients simply because CAR-Ts are helping them live longer. In other words, patients who didn’t get CAR-Ts might have died from their primary cancers before any possibility of developing new cancers later in life. As for that Carvykti case, Banerjee acknowledged that its CAR-positive nature and the fact it emerged just five months post-infusion definitely looked bad. But he argued it was still not a smoking gun. The case had other cancer-driving mutations in the cells that might predispose the patient to T cell malignancies, he noted. And the CAR inserted into a region of an entirely different gene. One way Banerjee said could confirm a causal link requires CAR insertion into an important gene with the cells becoming cancerous, which didn’t happen in the Carvykti case. Alternatively, Banerjee said he would also be convinced if there were very high vector copy numbers with chaotic CAR insertions everywhere, a phenomenon that had happened to earlier generations of candidates but not in any existing therapies. Banerjee also flagged the secondary cancer risks linked to other myeloma treatments. “I’ve actually never had a patient turn down [BMS’ Revlimid] or transplant purely for the second cancer risk, because everyone gets this, like, look, the cancer at hand is always a bigger problem than the theoretical cancer that may be years from now.”