Medical
PR Newswire | October 10, 2023
Immunic, Inc. a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases, today announced positive interim data from its phase 2 CALLIPER trial of nuclear receptor related 1 (Nurr1) activator, vidofludimus calcium (IMU-838), in patients with progressive multiple sclerosis (PMS). The Company believes that this data shows biomarker evidence that vidofludimus calcium's activity extends beyond the previously observed anti-inflammatory effects, thereby further reinforcing its neuroprotective potential.
Serum NfL responses were consistently observed for vidofludimus calcium across progressive MS disease and all subpopulations. In the overall PMS population at 24 weeks (N=203), vidofludimus calcium was associated with a 6.7% reduction from baseline in serum NfL, compared to a 15.8% increase over baseline in placebo (p=0.01, post hoc). At 48 weeks (N=79), vidofludimus calcium reduced serum NfL by 10.4% from baseline, compared to a 6.4% increase in placebo. Substantial reductions were also seen across all PMS subtypes, as well as in patients that show or do not show disease and/or magnetic resonance imaging (MRI) activity.
Although early, interim GFAP data also showed a promising signal: at 24 weeks (N=203), GFAP increased by 3.7% for vidofludimus calcium, and 4.4% for placebo. At 48 weeks (N=79), the change was only 2.7% for vidofludimus calcium, with a 6.4% increase for placebo. Progression of GFAP response is generally thought to evolve more slowly than NfL, and the Company believes that a longer follow-up may further strengthen this signal.
"Serum NfL has been consistently shown to capture disease activity and to predict future disability in MS. Vidofludimus calcium shows a separation in serum NfL over placebo in this interim analysis, an effect also seen across different subgroups," stated Prof. Jens Kuhle, M.D., Ph.D., Senior Physician, Head of Neuroimmunology Unit and Multiple Sclerosis Centre, University Hospital Basel, Switzerland. "Particularly remarkable, the non-active progressive MS population, which represents the highest unmet medical need in MS, also showed differences in NfL levels over this relatively short observation period in favor of vidofludimus calcium. Meanwhile, although longer follow-up is needed, the GFAP data set also shows a potential promising early signal. Overall, the interim biomarker data further support vidofludimus calcium's possible activity beyond an anti-inflammatory effect, which may be related to its potent Nurr1 activation."
"The clear separation observed in serum NfL for vidofludimus calcium over placebo in the PMS patient population represents another major step forward for, what potentially could be, a first-in-class Nurr1 activator for MS," commented Daniel Vitt, Ph.D., Chief Executive Officer and President of Immunic. "Although no head-to-head data is available, it is encouraging to see that vidofludimus calcium's improvement in NfL over placebo appears at least as good as, and is in fact numerically higher than that observed with historical studies of other therapeutic approaches for PMS. We believe that, if the top-line CALLIPER data, expected in April of 2025, continue to show a neuroprotective effect, we may be able to position vidofludimus calcium as the first oral treatment option for non-active SPMS. Additionally, the drug's first-in-class ability to activate Nurr1, a known neuroprotective target, should also significantly benefit our ongoing phase 3 ENSURE program in relapsing MS where prevention of disability progression independent of relapse activity (PIRA), serves as a key outcome."
"We are very pleased to see such strong improvements in serum NfL for vidofludimus calcium over placebo in the overall PMS population of this interim analysis, as well as across all PMS subtypes and in patients with and without disease activity, and with and without MRI activity. We even saw evidence in non-active SPMS, a population where the medical need for new therapies is high as there is currently no relevant treatment available in the US," added Andreas Muehler, M.D., Chief Medical Officer of Immunic. "Finally, we were also excited to see an encouraging early signal with GFAP. This is a newer biomarker which is thought to evolve more slowly and with lower amplitude than NfL, and longer follow-up will hopefully allow us to see even stronger results."
The Company believes that these results corroborate separate findings from its phase 2 EMPhASIS trial in relapsing-remitting multiple sclerosis (RRMS), where vidofludimus calcium was associated with a decrease in serum NfL at 24 weeks (-17.0% for 30 mg and -20.5% for 45 mg) as compared to baseline values, as contrasted with a 6.5% increase in serum NfL over baseline among placebo patients.
CALLIPER is a multicenter, randomized, double-blind, placebo-controlled phase 2 trial which enrolled 467 patients with primary PMS or active or non-active secondary PMS at more than 70 sites throughout North America as well as Western, Central and Eastern Europe. Patients were randomized to either 45 mg daily doses of vidofludimus calcium or placebo, and the trial's primary endpoint is the annualized rate of percent brain volume change up to 120 weeks. Key secondary endpoints include the annualized rate of change in whole brain atrophy and time to 24-week confirmed disability progression based on the expanded disability status scale (EDSS).
Anticipated MS Clinical Milestones
Top-line data from the phase 2 CALLIPER trial of vidofludimus calcium in PMS is expected in April of 2025.
Data from the interim analysis of the phase 3 ENSURE program of vidofludimus calcium in relapsing MS is expected in late 2024, with the top-line readout of the first of the ENSURE trials at the end of 2025.
The interim data of the phase 2 CALLIPER trial of vidofludimus calcium in PMS will be filed on a Form 8-K and discussed during the management presentation to be held tomorrow at 8:00 am ET. The presentation will also be accessible on the "Events and Presentations" section of Immunic's website at: https://ir.imux.com/events-and-presentations.
About Progressive Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease that affects the brain, spinal cord and optic nerve. In MS, myelin, the coating that protects the nerves, is attacked and damaged by the immune system. Thus, MS is considered an immune-mediated demyelinating disease of the central nervous system. Progressive multiple sclerosis (PMS) includes both primary progressive MS (PPMS) and secondary progressive MS (SPMS). PPMS is characterized by steadily worsening neurologic function from the onset of symptoms without initial relapse or remissions. SPMS is identified following an initial relapsing-remitting course, after which the disease becomes more steadily progressive, with (active SPMS) or without (non-active SPMS) other disease activity present.
About Vidofludimus Calcium (IMU-838)
Vidofludimus calcium is a small molecule investigational drug in development as an oral next-generation treatment option for patients with multiple sclerosis and other chronic inflammatory and autoimmune diseases. The selective immune modulator activates the neuroprotective transcription factor nuclear receptor related 1 (Nurr1), which is associated with direct neuroprotective properties. Additionally, vidofludimus calcium is a known inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells. This mechanism is associated with the anti-inflammatory and anti-viral effects of vidofludimus calcium. Vidofludimus calcium has been observed to selectively act on hyperactive T and B cells while leaving other immune cells largely unaffected and enabling normal immune system function, e.g., in fighting infections. To date, vidofludimus calcium has been tested in more than 1,400 individuals and has shown an attractive pharmacokinetic, safety and tolerability profile. Vidofludimus calcium is not yet licensed or approved in any country.
About Immunic, Inc.
Immunic, Inc. is a biotechnology company developing a clinical pipeline of orally administered, small molecule therapies for chronic inflammatory and autoimmune diseases. The company's lead development program, vidofludimus calcium (IMU-838), is currently in phase 3 and phase 2 clinical trials for the treatment of relapsing and progressive multiple sclerosis, respectively, and has shown therapeutic activity in phase 2 clinical trials in patients suffering from relapsing-remitting multiple sclerosis and moderate-to-severe ulcerative colitis. Vidofludimus calcium combines neuroprotective effects, through its mechanism as a first-in-class nuclear receptor related 1 (Nurr1) activator, with additional anti-inflammatory and anti-viral effects, by selectively inhibiting the enzyme dihydroorotate dehydrogenase (DHODH). IMU-856, which targets the protein Sirtuin 6 (SIRT6), is intended to restore intestinal barrier function and regenerate bowel epithelium, which could potentially be applicable in numerous gastrointestinal diseases, such as celiac disease, where it is currently in preparations for a phase 2 clinical trial. IMU-381, which currently is in preclinical testing, is a next generation molecule being developed to specifically address the needs of gastrointestinal diseases.
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Industry Outlook
GlobeNewswire | October 03, 2023
Amicus Therapeutics a global, patient-dedicated biotechnology company focused on discovering, developing, and delivering novel medicines for rare diseases, today announced that it has entered into a definitive agreement for a $430 million financing collaboration with funds managed by Blackstone. As part of the collaboration, Blackstone Life Sciences and Blackstone Credit have agreed to provide Amicus with a $400 million senior secured term loan facilitating a refinancing of existing debt and a $30 million strategic investment in Amicus’s common stock. The financing collaboration allows Amicus to grow revenues and move toward profitability while delivering on its mission for patients and its vision of being one of the leading biotechnology companies focused on rare diseases.
Bradley Campbell, President and Chief Executive Officer of Amicus Therapeutics, stated: “This new financing with Blackstone strengthens our balance sheet and financial profile by reducing the interest rate versus our current debt, pushing out the amortization schedule and extending the amortization period. This strategic investment demonstrates Blackstone's commitment to Amicus’ future and belief in the strong growth potential of Galafold and Pombiliti™ + Opfolda™ as we continue on our mission to develop medicines for people living with rare diseases.”
Key features of this transaction include
$400M senior secured term loan facility; interest rate at adjusted Term SOFR plus 6.25%, subject to a 2.50% floor on Term SOFR
$30M investment in Amicus common stock
Requires interest-only payments until late 2026 and matures in October 2029
The full amount of the loan and equity purchase will be available and fully drawn at the initial funding
The proceeds will be used to refinance Amicus’s existing debt and fund ongoing operations
Commenting on the arrangement, Craig Shepherd, Senior Managing Director with Blackstone Life Sciences and Brad Colman, Senior Managing Director with Blackstone Credit said: "Blackstone aims to provide customized financing solutions for the world’s leading biotech and pharma companies across therapeutic areas to support mission critical scientific innovation. We are excited to collaborate with Amicus and provide capital to advance their mission of bringing important new medicines to people living with rare diseases around the world."
Simon Harford, Amicus Chief Financial Officer, added: “Securing this financing with Blackstone as we launch Pombiliti™ + Opfolda™ around the world, allows us to better align our borrowing with anticipated cash flows while at the same time enhancing our ability to maximize access to our therapies for people living with rare diseases.”
Subject to completion of customary conditions, the loan is expected to be funded and the equity investment is expected to close on October 5, 2023.
About Amicus Therapeutics
Amicus Therapeutics is a global, patient-dedicated biotechnology company focused on discovering, developing and delivering novel high-quality medicines for people living with rare diseases. With extraordinary patient focus, Amicus Therapeutics is committed to advancing and expanding a pipeline of cutting-edge, first- or best-in-class medicines for rare diseases.
About Blackstone Life Sciences
Blackstone Life Sciences is an industry-leading private investment platform with capabilities to invest across the life cycle of companies and products within the key life science sectors. By combining scale investments and hands-on operational leadership, Blackstone Life Sciences helps bring to market promising new medicines and medical technologies that improve patients’ lives and currently has more than $8 billion in assets under management.
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Medical
GlobeNewswire | September 28, 2023
Repligen Corporation a life sciences company focused on bioprocessing technology leadership, announced that it has entered into a definitive agreement to acquire privately-held Metenova AB (Metenova) of Mölndal, Sweden. Metenova is projected to generate revenues of $24 million to $25 million for fiscal year 2023, led by the success of its magnetic mixing and drive train technologies that are widely used by global biopharmaceutical companies and contract development and manufacturing organizations (CDMOs). The company recently entered the single-use mixing market with the launch of its MixOne platform, leveraging the success of its existing stainless steel (repeat-use) product line.
Metenova is expected to contribute approximately $5 million in revenue to Repligen in the fourth quarter of 2023, and to contribute $25 million to $27 million in revenue in 2024, with 20%-25% revenue growth in 2025 forward. The acquisition is anticipated to be accretive to Repligen’s adjusted gross and operating margins in 2024, and to be accretive to adjusted earnings per share in 2025.
Over the past decade, Metenova has established market leadership through design innovation in magnetic mixing, with a state-of-the-art suite of both stainless steel and single-use impellers (mixer heads) and drive trains – key components of mixing vessels. The company offers a broad range of products, including high power solutions for efficient media and buffer preparation, and low shear solutions for gentle mixing of sensitive proteins. Metenova’s high performance aseptic mixing technologies are designed to minimize product damage and improve product yield and product consistency, contributing to improved ROI for customers. The company’s solutions are applicable to a wide range of small molecule and large molecule therapeutics and vaccines, including monoclonal antibodies, recombinant proteins, and cell and gene therapies.
Tony J. Hunt, President and Chief Executive Officer at Repligen said, “The addition of Metenova further strengthens our Fluid Management portfolio, with a product line that expands on the market success of our systems and fluid management assemblies and complements our recently acquired single-use bag business from FlexBiosys. We are excited to welcome the Metenova team to Repligen and we look forward to further developing and integrating their differentiated magnetic mixing technologies into our portfolio.”
Johan Westman, Chief Executive Officer at Metenova said, “We have made tremendous progress over the last ten years, building a market leading mixing portfolio. We are now at a stage in our development where we can benefit from more rapid expansion into the single-use market where many of our customers are scaling today. Repligen is the ideal partner for us to take this next step of growth and we look forward to working with our colleagues at Repligen to drive additional global demand for our single-use mixing products, while continuing to advance innovative single-use solutions for the industry.”
About Metenova AB
Metenova is a leading innovator and manufacturer of magnetic mixers for pharmaceutical and biotechnology use. We provide aseptic cutting-edge mixing technology for critical applications. Sales are mainly performed by distributors in over 30 countries with approximately one-third of sales in North America, one-third of sales in Europe and one-third of sales in Asia/ROW. Metenova recently entered the single-use mixing market with the launch of its MixOne platform, leveraging the success of its existing repeat-use (stainless steel) product line. Metenova is headquartered in Mölndal in the Gothenburg area and has approximately 50 employees.
About Repligen Corporation
Repligen Corporation is a global life sciences company that develops and commercializes highly innovative bioprocessing technologies and systems that enable efficiencies in the process of manufacturing biological drugs. We are “inspiring advances in bioprocessing” for the customers we serve; primarily biopharmaceutical drug developers and contract development and manufacturing organizations (CDMOs) worldwide. Our focus areas are Filtration and Fluid Management, Chromatography, Process Analytics and Proteins. Our corporate headquarters are in Waltham, Massachusetts, and the majority of our manufacturing sites are in the U.S., with additional key sites in Estonia, France, Germany, Ireland, the Netherlands and Sweden.
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