Global Roundup: Medtronic Kicks Off Aortic Stenosis Study in Japan

Ireland’s Medtronic enrolled the first patient in its EXPAND TAVR II pivotal trial assessing the supra-annular Evolut TAVR platform in patients with moderate, symptomatic aortic stenosis (AS), a population currently outside of guidelines and indications for transcatheter aortic valve replacement (TAVR).

The trial will assess the safety and efficacy of the Medtronic Evolut PRO+ TAVR System and guideline-directed management and therapy (GDMT) compared to GDMT alone. The study will be conducted in the moderate, symptomatic aortic stenosis patient population. It is possible the data from this study could be used to support future regulatory submissions to expand the current indications for the Evolut TAVR platform.

It is estimated that more than two million patients live with moderate aortic stenosis in the U.S. alone, which represents more than two times the population of patients with severe aortic stenosis. The current recommended management of patients with moderate AS includes periodic monitoring with transthoracic echocardiography every one to two years or any change in symptoms or findings.

Paul Soraija, the principal investigator of the EXPAND TAVR II study, said numerous patients live with different levels of aortic stenosis. Some may benefit from less invasive TAVR procedures even though they fall outside of the current indications. The study could provide new evidence of which patients can benefit from this procedure.

The first patient to be enrolled in the study is based at Shonan Kamakura General Hospital in Kamakura, Japan. The trial will be conducted across the globe, including sites in Australia, New Zealand, the U.S. and Canada. Medtronic anticipates enrolling up to 650 patients. The primary effectiveness endpoint of the study is the composite rate of all-cause mortality, heart failure event, aortic valve replacement or re-intervention at two years.

Elsewhere around the globe:

Enlivex Therapeutics: Based in Israel, Enlivex revealed a poster presentation of a survival benefit of Allocetra combined with immune checkpoint inhibition in preclinical mesothelioma. Data was presented at the International Society of Cell and Gene Therapy meeting. The poster was titled, “Allocetra-OTS, an Early Apoptotic Cellular Therapy Synergize with Chimeric Antigen Receptor (CAR) T Cell Therapy or Immune Check Point Inhibitor Against Peritoneal Solid Tumor.” Mesothelioma is a deadly solid cancers with few treatment options. Immune checkpoint inhibitors targeting CTLA4 and PD1 are FDA-approved as first-line treatments for unresectable malignant pleural mesothelioma patients.

SciSparc Ltd.: In Israel, SciSparc Ltd. announced its recently launched collaboration with Clearmind Medicine Inc., resulting in a provisional patent application related to a psychedelic combination therapy treating numerous binge behaviors. The patent application refers to the combination of SciSparc’s CannAmide with Clearmind’s MEAI, an innovative proprietary psychedelic treatment for addictions. The patent application followed preclinical studies that showed a significant dose dependent effect for MEAI treatment in reducing alcohol consumption of treated animals.

OncoHost: Another Israel-based company, OncoHost secured $35 million in Series C financing. Funds will be used to expand the company’s ongoing PROPHETIC trial, which uses the company’s machine-learning response profiling platform, PROphet. PROphet is a “disease navigator” used to provide early identification of an individual’s responsiveness to cancer therapy, analysis of treatment resistance mechanisms, and potentially available strategies to overcome this resistance. Clinical studies showed that PROphet has high accuracy in assessing non-small cell lung cancer (NSCLC) patient response at three months, six months and one year. The company’s multi-patented platform provides clinicians with potential combination strategies to overcome treatment resistance through one blood test pre-treatment. The funding round was led by ALIVE Israel HealthTech VC. Other participants included Leumi Partners, Menora Mivtachim, OurCrowd and other investors.

LianBio: Shanghai-based LianBio completed a Phase I pharmacokinetic study of mavacamten in healthy Chinese volunteers. The company reported that a single oral administration of mavacamten showed no new safety signals in Chinese healthy adult subjects. The Phase I data demonstrated favorable pharmacokinetics, safety, and tolerability profile. It was comparable to data seen in the Phase I pharmacokinetic study of mavacamten conducted by LianBio’s partner, MyoKardia. The study was conducted in parallel to an ongoing Phase III clinical trial of mavacamten in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). LianBio expects that the results of the pharmacokinetic trial, together with the results of its Phase III clinical trial, could enable it to submit a New Drug Application to the National Medical Products Administration to support regulatory approval in China.

AUM Biosciences: Based in Singapore, AUM Biosciences entered into a collaboration with Roche to assess AUM001, the company’s novel, highly selective MNK1/2 inhibitor, in combination with atezolizumab (Tecentriq), Roche’s anti-PD-L1 therapy, across multiple solid tumor indications, leading with NSCLC and urothelial cancer (UC). As a monotherapy, AUM001 demonstrated excellent safety, tolerability, and target engagement in two Phase I studies.

Olink Holding AB: Sweden’s Olink Holding announced that Oxford Genomics at the University of Oxford adopts the Olink technology and becomes the first Olink certified laboratory in the United Kingdom. The partnership is expected to enable novel techniques to unravel disease mechanisms using the Olink Explore platform. Olink Explore will be used to build a multiomics approach to mapping molecular mechanisms of complex diseases such as Parkinson’s and Alzheimer’s. Expertise in machine learning and bioinformaticians at Oxford’s Big Data Institute will be able to leverage these datasets to pinpoint novel targets and identify signatures to stratify patients.

Mereo BioPharma: London-based Mereo BioPharma Group plc announced positive topline data from the Phase II ASTRAEUS study, which is assessing the investigational oral neutrophil elastase (NE) inhibitor, alvelestat (MPH-966), in patients with severe alpha-1 antitrypsin deficiency-associated emphysema. At the high dose, alvelestat demonstrated statistically significant changes versus placebo in three primary biomarker endpoints associated with AATD-related lung disease (AATD-LD), blood neutrophil elastase activity, Aα-val360 and the elastin breakdown product, desmosine.

Evonetix Ltd.: Also based in the U.K., Evonetix was granted a European patent covering its unique Binary Assembly method for gene synthesis. According to the company, its novel semiconductor-based synthesis chip uses precise temperature control to manage the DNA synthesis cycle at thousands of individually addressable sites across the surface of the chip. The method allows for the assembly of long DNA molecules “on-chip” while also removing synthesis errors during the assembly process.

Virax BioLabs: Another London-based company, Virax, received ethical approval for its Analytical Performance Study for the Virax Immune COVID-19 Flow Cytometry Kit from the ethics committee of the Stichting Beoordeling Ethiek Biomedisch Onderzoek Foundation for the Assessment of Ethics of Biomedical Research. The committee is an independent medical research ethics committee for biomedical scientific research involving human subjects taking place within the Netherlands. The study will evaluate the technical performance of the Virax Immune COVID-19 Flow Cytometry Kit, an in-vitro diagnostic (IVD) test seeking detection of T-Cell immune responses to viral threats such as COVID-19 and its variants.

Avacta Group: London’s Avacta Group plc relocated its therapeutics division to a new London headquarters. The new office brings together its R&D teams to support the continued growth of the company’s pre-clinical and clinical development pipelines of innovative cancer therapies.

Iterum Therapeutics: Based in Ireland, Iterum Therapeutics met with the U.S. Food and Drug Administration to discuss plans to conduct an additional Phase III study that could support the potential resubmission of its New Drug Application for oral sulopenem etzadroxil-probenecid, a potential treatment of uncomplicated urinary tract infections.

Nykode Therapeutics: Norway-based Nykode Therapeutics AS announced positive interim results from its Phase II VB C-02 trial of VB10.16, which is being assessed in combination with the PD-L1 inhibitor atezolizumab in patients with HPV16-positive advanced cervical cancer. Interim results from 39 patients with a median follow up of 6 months show an ongoing response rate of 21%, including two patients who achieved a complete response and six who achieved a partial response. Data also showed a very high disease control rate of 64%. The trial enrolled a heavily pre-treated patient population, with more than two thirds of the patients having received at least two previous systemic lines of treatment.

AC Immune SA: Based in Switzerland, AC Immune announced data showing its ACI-24 anti-Abeta vaccine was found to be safe and elicited an immune response in a Phase Ib clinical trial in adults with DS. Data was published in JAMA Neurology. This is the first anti-Abeta vaccine study conducted with people living with DS.

Evaxion Biotech A/S: Denmark-based Evaxion said it successfully produced all batches of personalized cancer immunotherapies for all patients enrolled in the Phase I/IIa clinical trial of EVX-02 in adjuvant melanoma.

Germitec: Based in France, Germitec completed a financing round of €11 million. Funds will be used to launch an international commercial expansion plan across strategic markets, including the United States.