A Parasite/Bacteria Coinfection that Provides Protection to the Human Host

It has been known for decades that parasitic infections have a dramatic effect on the human immune system. For instance, some evidence suggests that certain allergic reactions are due, in part, to IgE molecules responding to antigens that are similar to proteins found on various parasitic worms, causing the immune system to overreact. What has been less well understood is the immune response to coinfections of parasites and pathogenic bacteria like Helicobacter pylori. Now, a new study from investigators at the Technical University of Munich (TUM) has completed the first study of the effects of simultaneous infection with blood flukes (schistosomes) and H. pylori—a common occurrence in some parts of the world. Findings from the new study were published recently in Cell Reports through an article titled “Concomitant Infection of S. mansoni and H. pylori Promotes Promiscuity of Antigen-Experienced Cells and Primes the Liver for a Lower Fibrotic Response.” Around 240 million people worldwide are afflicted with schistosomiasis, an illness caused by flatworms of the genus schistosoma, commonly known as blood flukes. These parasites generally enter the human body with water from lakes, ponds, or rivers. Worms, larvae, and eggs are transported to various organs in the body through the bloodstream. The species Schistosoma mansoni is especially damaging to the liver, where it causes cirrhosis.

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Capsida Biotherapeutics Enters Strategic Collaboration With Kate Therapeutics to Manufacture KateTx's Next-Generation Gene Therapies

PR Newswire | October 05, 2023

Capsida Biotherapeutics Inc. and Kate Therapeutics announced a strategic partnership to leverage Capsida's expertise and adeno-associated virus (AAV) manufacturing capabilities to enable KateTx's initial internal portfolio of muscle and heart disease programs. Under the terms of the agreement, Capsida will provide GMP manufacturing of KateTx's gene therapies as the medicines advance through preclinical and clinical development. In return, Capsida will receive undisclosed funding for the term of the agreement. KateTx's publicly disclosed internal programs include myotonic dystrophy type 1 and facioscapulohumeral muscular dystrophy, which are two of the leading causes of adult-onset muscular dystrophy. "Capsida possesses end-to-end expertise – which includes AAV capsid engineering, preclinical, clinical, and state-of-the-art manufacturing," said Peter Anastasiou, chief executive officer (CEO) of Capsida Biotherapeutics. "We are thrilled to be able to leverage our established capabilities in AAV manufacturing and support a peer company to reach patients in a complementary space, while continuing to advance our own internal and partnered pipeline in CNS and ophthalmology." "KateTx is leading the way in developing capsid and cargo combinations to address muscle and heart diseases in ways that have not been previously possible," said Kevin Forrest, Ph.D., president and CEO of Kate Therapeutics. "Capsida's exceptional AAV manufacturing capabilities allow us to build our pipeline, de-risk our programs, and advance them into the clinic in the most rapid manner possible, so we can bring much-needed therapies to patients quickly." "This collaboration between Capsida and KateTx leverages complementary expertise and overlapping needs across both innovative companies to advance programs in a capital-efficient manner. Capsida has established first-in-class engineered AAV manufacturing capabilities applicable across broad therapeutic areas, and this partnership with KateTx aims to bring these next-generation gene therapies to patients sooner than with traditional approaches," said Beth Seidenberg, M.D., co-founding managing director at Westlake Village BioPartners, member of the board of Capsida, and chair of the board at KateTx. About Capsida Biotherapeutics Capsida Biotherapeutics is an integrated gene therapy company developing treatments for rare and common diseases across all ages. Capsida's new class of engineered adeno associated virus (AAV)-based delivery technologies enables a broad range of therapeutic modalities, including DNA, RNA, gene editors, vectorized antibodies and other genetic cargoes, to be systemically delivered to specific organ systems while simultaneously limiting exposure to non-targeted organs. Capsida's proprietary capsid engineering and broad IP estate allows for identification and development of capsids with tropism for any tissue or cell type. The company's initial focus has been delivering therapeutic cargoes intravenously to the central nervous system (CNS) with high transduction levels to the desired tissues and cells. The company is developing a pipeline of both wholly owned programs in CNS and partnered programs with AbbVie (CNS and broad range of ophthalmic disorders), Lilly (CNS), and CRISPR Therapeutics (CNS). Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. About Kate Therapeutics Kate Therapeutics (KateTx) is a patient-focused biotechnology company developing adeno-associated virus (AAV)-based gene therapies to treat genetically defined muscle and heart diseases. The company is applying novel technology platforms that directly address the key limitations of current gene therapies, including tissue-specific delivery and gene regulation. These breakthroughs have the potential to improve the efficacy and safety of gene therapies and enable the pursuit of a broader set of targets that are otherwise difficult to drug with current technologies.

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BenevolentAI Signs Strategic Collaboration with Merck

Business Wire | September 26, 2023

BenevolentAI a leader in the development of advanced AI that accelerates biopharma discovery, announces that it has signed a strategic collaboration with Merck, a leading science and technology company headquartered in Darmstadt, Germany. The collaboration will enable Merck to leverage BenevolentAI’s powerful end-to-end AI platform capabilities and gain access to an expert team of interdisciplinary drug discovery scientists with the aim of identifying and developing innovative compounds, through Hit Identification (Hit ID) to pre-clinical stage. BenevolentAI will leverage its suite of AI chemistry design tools, in combination with its fully equipped wet lab facility in Cambridge (UK), to deliver small molecule drug development candidates into the Merck pipeline, ready for onward pre-clinical and clinical development. Under the terms of the agreement, BenevolentAI will be eligible for payments of up to $594 million, consisting of a low double-digit million dollar upfront payment on signing and then potentially discovery, development and commercial milestones. Tiered royalties will also be payable on net sales of any commercialised products. Joanna Shields, Chief Executive Officer of BenevolentAI, said: “Our strategic collaboration with Merck exemplifies BenevolentAI’s unique capability to leverage AI to accelerate drug discovery. Our proprietary technology and extensively validated approach of combining AI, molecular biology, medicinal chemistry, and in vivo pharmacology supports the discovery of innovative drug candidates in fewer cycles. We look forward to working with the Merck team and are excited at the opportunities in our partnership.” Public disclosure of inside information in accordance with article 17(1) of the Regulation (EU) No 596/2014 on market abuse (Market Abuse Regulation) About BenevolentAI BenevolentAI is a leading developer of advanced artificial intelligence technologies that unlock the value of multimodal data, surface novel insights, and accelerate biomedical discovery. Through the combined capabilities of its AI platform, its scientific expertise, and wet-lab facilities, the Company is developing an in-house drug pipeline of high-value assets. The Company is headquartered in London, with a research facility in Cambridge (UK) and a further office in New York.

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Immunic Reports Positive Interim Data from Phase 2 CALLIPER Trial of Vidofludimus Calcium in Progressive Multiple Sclerosis

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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