University of Missouri-Kansas City

Arimoclomol was originally submitted to the FDA in July 2020 but was rejected almost a year later because the agency questioned aspects of the single clinical trial used to support the application. Zevra Therapeutics’ rare disease drug seems to be on the path to approval this fall after gaining the backing of an FDA advisory committee, although the experts were split, with some voting yes simply to address an unmet need.The agency’s Genetic Metabolic Diseases Advisory Committee voted 11 to 5 in favor of arimoclomol on a questions of whether the evidence supports the drug’s efficacy to treat patients with Niemann-Pick disease type C at the Friday meeting. The rare, genetic lysosomal storage disease prevents the body from moving and using cholesterol and other lipids in cells. This leads to a build-up of cholesterol and other lipids in the liver, spleen or lungs.There are no approved treatments for the disease, according to the FDA. Patients typically receive anti-seizure medicine and other supportive care.The FDA is set to decide on the drug’s approval by September 21. While the agency does not have to do exactly as the committee suggested, it does typically heed the advice of its expert panels.Arimoclomol was originally submitted to the FDA in July 2020 but was rejected almost a year later because the agency questioned aspects of the single clinical trial used to support the application. While the FDA can approve a drug based on evidence from just one trial, the applicant must show that the test meets the bar of being considered a “single adequate and well-controlled clinical trial.”Zevra submitted data from a 12-month, randomized double-blind, placebo-controlled study called CT-ORZYNPC-002. The main goal was a measure of disease severity called the 5-domain NPC Clinical Severity Scale (5DNPCCSS), which assesses clinical outcomes for the disease, including swallowing, speech, fine motor, ambulatory, and cognitive functioning. In the complete response letter from 2021, the FDA questioned the interpretability of the 5DNPCCSS, specifically its validity and reliability. There were also concerns with the prespecified primary analysis of the 5DNPCCSS endpoint and lack of statistical significance in the FDA’s own post hoc analyses of the 5DNPCCSS endpoint. And finally, the agency flagged “weak and contradictory confirmatory evidence of effectiveness,” specifically inconsistent results in mouse studies.Zevra was asked to address the swallow scores and whether a rescoring of the scale or alignment with a National Institutes of Health measure of swallowing would be better. The company was also directed to produce more evidence to support the interpretation and use of the 5DNPCCSS score, check whether evidence from the existing clinical trial would be good enough to support a re-application and “bolster the confirmatory evidence.”With that long to-do list, Zevra returned to the FDA in December 2023 with a rescored scale and more results from the study, including data from an open-label expansion phase. Zevra also submitted a natural history comparison of the disease from the NIH and more preclinical evidence.At the advisory committee meeting, the FDA wanted the experts to consider the validity of the new four-point scale and the post-hoc exploratory revision of the primary efficacy endpoint. The committee was also tasked with considering the uncertainty of the estimated treatment effect on the revised primary endpoint; adequacy of the additional clinical and nonclinical evidence; and the strength of the overall evidence to support the efficacy of arimoclomol.After the vote, many of the panel members said they were torn on the efficacy package, but ultimately Zevra's therapy passed.  “I voted yes but it was a very reluctant yes. I found the effect size to be small and the strength of the data to be weak, but overall the bulk of the data favored a slightly positive effect,” said Jonathan Mink, M.D., Ph.D., a private consultant. “I think the unmet need is very clear. I’m not sure this meets that need, but again on balance I voted yes.”Priya Kishnani, M.D., also voted yes, noting the clinical unmet need, very good safety profile and trends toward efficacy. Kishnani is a professor of pediatrics at the Duke University Medical Center. Jean Baptiste Le Pichon, M.D., Ph.D., voted yes as well, but said he did not rely on the nonclinical data that was submitted to make his decision. Le Pichon, a professor of pediatrics and the associate director for the Division of Neurology at Children's Mercy Kansas City and the University of Missouri Kansas City, said that the data were “not convincing.”When looking at the clinical data, however, Le Pichon was convinced that there was enough of an effect to recommend approval of arimoclomol.“It was not an enormous effect but it was an effect that was clinically significant,” Le Pichon said.He acknowledged that he may have broken the rules of the vote by ignoring the preclinical evidence. But the clinical data was what mattered the most to him.“If I was forced to vote no just because the non-clinical data was not convincing then I went against the rules but this is where my clinical intuition was and I am a clinical at heart,” Le Pichon said.Gerard Berry, M.D., professor of pediatrics at Harvard Medical School, voted yes, noting that the testimony of the families that arimoclomol led to a beneficial effect was moving.“Taking all data together it made sense that this is having a beneficial effect,” Berry said.Kenneth Fischbeck, M.D., who voted no, was not convinced that the new data helped the re-application, calling it “problematic.”“I think it could be done better. I think there’s a real unmet need in this space. And I think this drug or one like it could be effective but I haven’t seen the data yet to make a convincing case,” Fischbeck said in explaining his vote.Like Berry, Robert Alexander, M.D., was moved by the patient testimony, but said it was not enough to convince him that the trial showed benefit. He “had to rely on the data from the controlled trial and I didn’t feel like it really rose to the level of substantial evidence of efficacy on its own.” Alexander is the chief scientific officer for the Alzheimer’s Prevention Initiative at the Banner Alzheimer’s Institute and a research professor at the University of Arizona College of Medicine.

MADISON, Wis.--( BUSINESS WIRE )--Nimble Therapeutics announced that Dan Flynn and Brian Cali have joined the company’s Board of Directors. Both bring deep entrepreneurial and drug development track records that will guide Nimble as it continues to pursue its internal pipeline. Dr. Flynn has over 40 years of experience in the discovery and development of high-impact medicines. He recently retired from Deciphera Pharmaceuticals, a company he founded in 2003. At Deciphera, Dr. Flynn held positions of Chief Executive Officer, Executive Vice President, and Chief Scientific Officer where he oversaw the progression of several molecules through clinical trials, including Qinlock® for the treatment of gastrointestinal stromal tumors. Before founding Deciphera, Dr. Flynn held senior roles with various companies including Millennium Pharmaceuticals, Amgen Inc. and the Monsanto Company, G.D. Searle Unit. Dr. Flynn is currently Adjunct Professor of Medicinal Chemistry at the University of Kansas-Lawrence. He has served as the National Chair for the Division of Medicinal Chemistry of the American Chemical Society, is an American Chemical Society Fellow, and founder of the Bioorganic and Medicinal Chemistry Foundation. He is a member of the Board of Directors and Scientific Advisory Boards of several biotech companies. Dr. Flynn received both his B.S. in pharmacy and Ph.D. in medicinal chemistry from the University of Kansas and completed post-doctorate training in synthetic organic chemistry at Indiana University. Dr. Cali has over 25 years of pharma biotech experience. He co-founded Ironwood Pharmaceuticals in 1998 where he held leadership roles across R&D and corporate development and helped drive the company’s transformation from an early discovery stage startup to a commercial stage company with a market leading gastrointestinal (GI) disease product (Linzess ® ) and a diverse pre-commercial pipeline. Brian also led the investor engagement and financing efforts that enabled the creation of Cyclerion, an Ironwood spinout, in 2019. He currently serves on the Board of Directors of Jnana Therapeutics, a role he has held since 2018. He holds a B.S. from Cornell University, a Ph.D. in Cell and Molecular Biology from the University of Wisconsin-Madison and was a postdoctoral fellow at the Whitehead Institute. "We are pleased to welcome Daniel and Brian to our Board of Directors at this important stage of Nimble’s evolution," said Jigar Patel, founder & CEO of Nimble Therapeutics. "Both are renowned pharma biotech entrepreneurs, having founded and successfully led companies that have developed novel small molecule or peptide-based drugs. We look forward to their guidance as we work to bring breakthrough medicines into clinical development, and ultimately to patients in need.” "Daniel and Brian are valuable additions to Nimble’s board, and their expert guidance will be paramount to the company as it continues to concentrate on developing and progressing its internal pipeline,” said Board Chair Dan Zabrowski. “It is an exciting time to be joining Nimble as they seek to leverage their incredibly versatile technology and team to develop best-in-class / first-in-class peptide-based medicines for the treatment of important diseases.” said Dr. Flynn. “Nimble has a paradigm shifting platform and I am impressed with what they have already accomplished. I look forward to helping the company as their efforts toward their own pipeline intensify, and they push towards the clinic and beyond.” said Dr. Cali. About Nimble Therapeutics Nimble is a biotechnology company dedicated to delivering on the promise of peptide therapeutics. Leveraging a paradigm-shifting peptide drug discovery and development engine, Nimble is advancing its internal pipeline and continues to support several partnered programs. The Nimble platform combines massively parallel solid-phase synthesis, unrivaled chemical and structural diversity, sophisticated assays, and powerful machine learning and computational methods. Nimble is located in Madison, WI and Philadelphia, PA. For more information, visit www.nimbletherapeutics.com .

Commitment to make life-saving products to treat life-threatening hypovolemia due to sepsis and blood loss available in Sub-Saharan Africa where there is outsized demand. Targeted $20M Series B Round to include Sub-Saharan Africa in product development. Partnering with Propelevate to drive Sub-Saharan Africa strategy. KANSAS CITY, Mo., Feb. 22, 2024 /PRNewswire/ -- Life sciences company Vivacelle Bio today announced Sub-Saharan Africa as a priority region for its life-saving alternative to fluid resuscitation to treat hypovolemia caused by severe sepsis, septic shock, or blood loss. Vivacelle Bio's lifesaving cardiovascular support fluids (VBI-S and VBI-1), both comprised of phospholipid nanoparticles, can be used to treat the refractory hypovolemia and hypotension that occur in severe sepsis and septic shock, and used instead of blood to correct hypovolemia from blood loss such as after major vehicle collisions and postpartum hemorrhage. Vivacelle Bio is partnering with Propelevate to drive the Sub-Saharan Africa strategy, which is fully integrated into its Series B financing round. Globally, sepsis kills ~11M people each year. Young children in Sub-Saharan Africa have outsized rates of sepsis death from neonatal sepsis, and sepsis caused by respiratory infection, diarrheal disease, and malaria. A child born in sub-Saharan Africa is nearly 8 times more likely to die in the first month of life than a child born in the US. Likewise, seventy percent of pregnancy-related deaths globally occur in Sub-Saharan Africa. Annually more than 75,000 women in the region die from postpartum hemorrhage or maternal sepsis. Vivacelle Bio's use of phospholipid nanoparticles to raise the blood pressure in patients with life-threatening hypovolemia due to blood loss, sepsis and septic shock is unprecedented. A successful phase 2a clinical trial of VBI-S, the formulation designed for treating hypovolemia due to septic shock, was recently completed. The fluid restores intravascular volume and absorbs nitric oxide, a gas made by the body that is largely responsible for the drop in blood pressure that is not responsive to current therapy. The evidence from the clinical trial showed that VBI-S is safe for patients while it increases blood pressure and reverses organ failure even when standard therapy has failed. This is the first-time in 20 years that a phase 2 or phase 3 trial in septic shock has succeeded in meeting all of its efficacy endpoints. VBI-1, designed for blood loss, also absorbs nitric oxide, and protects vital organs from reperfusion injury. Pre-clinical studies show that VBI-1 has greater efficacy than blood or standard of care fluids in raising blood pressure after severe hemorrhagic shock. Blood and other fluids promote reperfusion injury to vital organs while VBI-1 prevents this organ damage. The current $20M Series B round includes funding for a Global Pediatric Phase III trial for VBI-S, and two Phase IIA trials for VBI-1, which will integrate sites in Sub-Saharan Africa to ensure the efficacy of both products in diverse contexts. Vivacelle Bio Co-Founder Dr. Cuthbert Simpkins, MD, Chief Innovation Officer of Vivacelle Bio and Sosland Missouri Endowed Chair in Trauma Services at the University of Missouri, Kansas City (UMKC) School of Medicine, says "VBI-S and VBI-1 can be used in any context where there is a health worker able to administer IV fluids. VBI-S has shown to be more effective than vasopressors at addressing septic shock, without the side effects such as gangrene of fingers and toes. Moreover, VBI-S carries oxygen and is shown to improve lung oxygenation, and reverse elevated creatinine in septic patients. Both VBI-S and VBI-1 are shelf stable for at least a year at room temperature with VBI-S currently having more than 2 years stability at room temperature. VBI-1 circumvents many of the challenges of blood transfusions: the challenges of securing blood donors, the need to type, to maintain cold chain, the short shelf-life, and the risk of disease transmission." Harven DeShield, JD, PhD, the CEO of Vivacelle Bio commented, "Being born in Liberia, and raised in Liberia, Côte d'Ivoire and Tanzania, the critical value proposition of VBI-S and VBI-1 being readily affordable and available in Africa is not only of immense personal importance, but also provides a holistic, strategic vehicle to address persistent health inequities in Africa related to treatment of shock and trauma." Dr. Angela James, Senior Advisor for 2Flo Ventures, a Chicago-based startup studio and venture capital firm, and investor in Vivacelle Bio, echoed the importance of the impact of addressing the global unmet need for people with sepsis and septic shock having equitable access to safe and effective treatments. "Vivacelle Bio is poised to bring life-changing drugs to patients and their families in a region which has not been given equitable access to effective therapies is a great opportunity from both a healthcare and business perspective." Through partnership with Propelevate, Vivacelle Bio will engage global health funders and stakeholders during final stages of product development, and Propelevate will drive Vivacelle Bio's go-to-market strategy for African markets upon regulatory approval. "We are excited to partner with Vivacelle Bio because of their commitment to Sub-Saharan Africa. Life sciences companies typically think about the region as an afterthought. Vivacelle Bio is already taking specific needs in the region into account in product development and laying the groundwork for eventual local manufacturing to ensure wide availability of its life-saving products," said Propelevate's Managing Director Krisila Benson. This work was supported by the Naval Medical Research Command (NMRC) - Naval Advanced Medical Development (NAMD) Program under MTEC award 20-02-NavyMultiTopic-002. About MTEC The Medical Technology Enterprise Consortium (MTEC) is a 501(c)(3) biomedical technology consortium collaborating under an Other Transaction Agreement (OTA) with the U.S. Army Medical Research and Development Command (USAMRDC) that serves those who serve our nation. For more information about MTEC, visit mtec-sc.org. About Vivacelle Bio: Vivacelle Bio () is a life sciences company that utilizes patented phospholipid nanoparticle technology to design products that increase the survivability of critically-ill patients. In addition to VBI-S and VBI-1, Vivacelle Bio has a pipeline of products at various stages of development applicable to a range of health areas including reperfusion injury, organ preservation and transplantation, multiple organ dysfunction syndrome and hyperprocalcitonemia. Vivacelle Bio has raised approximately $10.9M in seed and Series A1-A3 funding, including from the US Department of Defense, the US National Institutes of Health, and 2Flo Ventures. About Propelevate: Propelevate () is a consulting firm working at the intersection of the private sector and social impact. Propelevate has experience bringing new health products to market in Africa and Asia, raising tens of millions of dollars in global health financing, and brokering successful partnerships between commercial and development actors. SOURCE Vivacelle Bio