Dynacure SA

Astellas is continuing to investigate how AT132 exacerbates liver conditions. Astellas has shared a detailed look at the four deaths in its AT132 gene therapy clinical trial. Writing in The Lancet Neurology, the drugmaker explained that the liver toxicity seen in the trial differs from cases linked to other therapies—and made the case that the drug can still provide transformative clinical benefits.   The paper presents data collected in the ASPIRO trial through Feb. 28, 2022. By that time, the FDA had put the study of children with X-linked myotubular myopathy (XLMTM), a life-threatening condition that causes muscle weakness and respiratory distress, on clinical hold for a second time in response to a fourth death. The study remains on hold.  Astellas shared details of the events leading up to the four deaths in the paper. All four patients had cholestatic liver failure at the time of death. Five of the 20 surviving dosed participants suffered serious treatment-related hepatobiliary adverse events. Analyses of antibodies, cellular markers and other factors suggest the adverse events weren’t caused by immune responses, although Astellas lacks the data to draw firm conclusions. The four patients who died all received immunosuppressive regimens, but the drugs had no apparent benefits. Liver toxicities caused by other gene therapies have responded to immune-modulating therapies. Assessments of the surviving participants revealed liver laboratory abnormalities before and after dosing with AT132. The abnormalities included features thought to be linked to intrahepatic cholestasis, a liver condition that causes the buildup of bile acids, and may have been implicated in the deaths.  Going into the clinical trial, the potential link between XLMTM and cholestatic liver disease was “largely unrecognized,” according to the researchers. The paper cites multiple case series and reports that have described the link since Astellas and the FDA paused ASPIRO, plus details of Dynacure’s decision to stop a trial of an antisense nucleotide in a related myopathy in response to liver enzyme elevations. Astellas is continuing to investigate how AT132 exacerbates liver conditions. Addressing the safety issues may unleash a therapy that showed some clinical promise in the trial. Astellas linked the therapy to improvements on respiratory parameters, including reductions in ventilator use, that the researchers see as evidence AT132 can provide “transformative clinical improvements.” The investigations may benefit Astellas even if it fails to resurrect AT132. In June, the drugmaker struck a deal for exclusive rights to Kate Therapeutics’ preclinical XLMTM gene therapy KT430, which uses a novel MyoAAV capsid to deliver a functional copy of the MTM1 gene. AT132 uses an AAV8 vector to deliver the gene.

LEUVEN, Belgium and STRASBOURG, France and PHILADELPHIA, June 15, 2023 /PRNewswire/ -- Flamingo Therapeutics ("Flamingo") today announced that it has been awarded a research grant of €1.7 million by Flanders Innovation & Entrepreneurship (VLAIO). The award represents the funding at 60% of a €2.9 million project. Funding from the grant will be used to advance Flamingo's RNA-targeting oncology portfolio, including translational research for its lead clinical program, danvatirsen in Phase II in head and neck squamous cell carcinoma, and preclinical work on its long non-coding RNA (LncRNA) program targeting MALAT-1. "We are thrilled to be recognized by VLAIO as a company who is innovating and disrupting the oncology landscape with our RNA-targeting approach," said Floor Stam, Head of Corporate Development and Operations. "This award provides further validation of our approach in creating a meaningful pipeline of programs that target undruggable transcription factors and non-coding RNA, such as STAT3 and MALAT-1. We thank VLAIO for their partnership and collaboration in helping us build a leading oncology company based on RNA therapeutics." Danvatirsen is an antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two Phase II clinical studies. Danvatirsen binds to STAT3 mRNA, inducing breakdown of the transcript. Currently, danvatirsen is planned to continue Phase 2 clinical development for head and neck squamous cell carcinoma to advance the program through key clinical milestones and data readouts. Flamingo is also advancing FTX-001, Flamingo's most advanced long non-coding RNA (LncRNA) program which targets MALAT-1, through readiness for Phase 1 in solid tumors. LncRNAs are a large and untapped class of disease-causing targets within the "dark matter" of the human genome. Receipt of this funding follows the merger between Flamingo and Dynacure, announced in March 2023. About VLAIO Flanders Innovation & Entrepreneurship (Agentschap Innoveren & Ondernemen - VLAIO) is a Flemish Government agency that stimulates and supports R&D activities by innovative entrepreneurs and companies. More information: About Flamingo Therapeutics Flamingo is pioneering RNA-targeted therapies for oncology with state-of-the art chemistries and a clinical-stage pipeline targeting undruggable transcription factors and splice variants. Flamingo has an alliance with Ionis Pharmaceuticals and is supported by well-known biotechnology investors including Andera Partners, Bpifrance Large Venture, Bpifrance through its FABS and Fonds Biothérapies Innovantes et Maladies Rares funds, Eurazeo - Kurma Partners, Perceptive Advisors, PMV, Pontifax, Sphera, funds managed by Tekla Capital Management LLC and VIB. Flamingo is initiating a Phase II trial 'PEMDA-HN' evaluating the STAT3 targeting agent danvatirsen, in combination with pembrolizumab, in patients with head and neck squamous cell carcinoma (HNSCC). For more information on Flamingo, please visit: . Please engage with us on LinkedIn: . Flamingo Media and Investor Contact: Amy Conrad Juniper Point (858) 366-3243 [email protected] SOURCE Flamingo Therapeutics

We’ll be keeping an eye out for everything from the Big Pharma bolt-ons and blockbusters to the reverse mergers and biotech-on-biotech buyouts. Acquisitions are back, biotech. After a stagnant year with pharma sitting on a heap of cash, the fruits of in-person business development meetings are beginning to ripen. And so today, Fierce Biotech launches the M&A Tracker, your one-stop shop for dealmaking in the biopharma universe. We’ll be keeping an eye out for everything from the Big Pharma bolt-ons and blockbusters to the reverse mergers and biotech-on-biotech buyouts. Here’s hoping the remaining three quarters of 2023 are filled with exciting deals that can pull the biotech industry out of its cloud to brighter days. https://omny.fm/shows/the-top-line/february-10-2023/embed   May XinThera Date: May 9 Buyer: Gilead Sciences Price: Undisclosed Gilead is picking up PARP1 and MK2 inhibitor specialist XinThera for an undisclosed sum, adding a few early-stage prospects to its pipeline. The goal is to find a match for breast cancer med Trodelvy to take on AstraZeneca’s Lynparza. Story   Iveric Bio Date: May 1 Buyer: Astellas Pharma  Price: $5.9 billion Astellas is paying a cool $5.9 billion to enter an eye disease niche with the acquisition of Iveric Bio. The biotech is awaiting an FDA decision for the approval of avacincaptad pegol, a complement C5 protein inhibitor that reduced the rate of geographic atrophy progression in a phase 3 clinical trial. Story April Bellus Health Date: April 18 Buyer: GSK Price: $2 billion GSK has bought out Bellus Health for its phase 3 chronic cough treatment camlipixant, a rival to Merck & Co.'s stalled candidate gefapixant. The Big Pharma believes that, even if camlipixant arrives on the market years after Merck does, a multibillion-dollar opportunity awaits. Story   Satsuma Pharmaceutical Date: April 17 Buyer: Shin Nippon Biomedical Laboratories Price: $0.91 per share, estimated $30 million* Satsuma Pharma was in need of a helping hand to move its migraine spray forward, and the company behind the nasal spray tech stepped up with a 91 cents per share offer. Story  * Deal value calculated by share price multipled by outstanding shares.    Prometheus Biosciences Date: April 17 Buyer: Merck & Co. Price: $10.8 billion Prometheus created a lot of buzz with midstage data for bowel disease candidate PRA023 late last year. Merck emerged victorious with an offer of $10.8 billion, but it wasn't the only Big Pharma that tried. Story StrideBio Date: April 5 Buyer: Ginkgo Bioworks Price: Undisclosed Ginkgo is bolstering its gene therapy capabilities with the purchase of AAV gene therapy capsid specialist StrideBio. The goal of the acquisition is to gain the biotech's intellectual property, not to get into drug development. The company's TRX-330 program for arrhythmogenic right ventricular cardiomyopathy will be sold off. Story March Diffusion Pharmaceuticals Date: March 30 Buyer: EIP Pharma Price: N/A EIP needed help to bring an ex-Vertex molecule into phase 2, and Diffusion Pharma proved to be the lifeline. The two companies decided to merge to create one publicly listed company to complete a clinical trial in dementia with Lewy bodies. Story   Jounce Therapeutics Date: March 27 Buyer: Concentra Biosciences Price: $1.85 per share, estimated $97.4 million* Jounce and Redx planned to ride out the biotech markets together in a reverse merger. Jounce was expected to contribute at least $130 million to the combined group to fund Redx's ROCK2 inhibitor RXC007. But months later, Jounce bounced and instead took a deal from Concentra Biosciences. Story * Deal value calculated by share price multipled by outstanding shares.  Dynacure Date: March 2 Buyer: Flamingo Therapeutics Price: Undisclosed Flamingo Therapeutics picked up Dynacure in a deal that will see the combined companies work together to develop RNA-targeted oncology therapies. Dynacure CEO Stéphane van Rooijen, M.D., will lead the combination with Flamingo CEO Michael Garrett at his wing as chief operating officer. Story February Adamis Pharmaceuticals Date: Feb. 28 Buyer: DMK Pharmaceuticals Price: Undisclosed Another biotech searching for help after a rough go in the clinic, Adamis accepted a merger with neurology-focused DMK Pharmaceuticals. Story   Infinity Pharmaceuticals Date: Feb. 23 Buyer: MEI Pharma  Target:  Price: N/A MEI Pharma and Infinity Pharma will join forces in a biotech-to-biotech merger that will see a newly named company rise from the ashes. Cambridge, Massachusetts-based Infinity will become a wholly owned subsidiary of MEI, whose shareholders will own approximately 58% of the company. Story VBL Therapeutics Date: Feb. 23 Buyer: Notable Labs Price: N/A 2022 didn't go well for VBL Therapeutics, and so the immune- and inflammatory-disease-focused biotech will merge with cancer-focused platform company Notable. Story   Erytech Pharma Date: Feb. 15 Buyer: Pherecydes  Price: N/A A new company focused on extended phage therapies will emerge from the combination of Erytech Pharma and French biotech Pherecydes. Story   Immunorizon Date: Feb. 2 Buyer: Purple Biotech Price: Up to $100 million Privately held Immunorizon will come under the wing of Purple, which focuses on tumor immune evasion and drug resistance. Purple has two lead assets in the pipeline: NT219 and CM24 for solid tumors and pancreatic ductal adenocarcinoma, respectively. Story January Concert Pharmaceuticals Date: Jan. 19 Buyer: Sun Pharmaceuticals Price: $576 million Sun Pharma has plunked down a cool $576 million to go up against Eli Lilly's approved alopecia treatment with Concert's JAK inhibitor. Story   Flame Biosciences Date: Jan. 17 Buyer: Leap Therapeutics Price: $86 million Leap Therapeutics hopped over to pick up Flame Biosciences for $86 million on a day busy with deals, adding another candidate to its pipeline. Story   4SR Biosciences Date: Jan. 17 Buyer: hC Bioscience Price: Undisclosed In a merger of equals, 4SR Bio's sequencing technology will be brought over to hC Bio to identify more potential therapeutics. Story Angion Biomedica Date: Jan. 17 Buyer: Elicio Therapeutics Price: N/A Elicio Therapeutics caught a ticket to the public markets via a reverse merger with Angion Biomedica to continue pushing a cancer vaccine into phase 2 trials. Story   CinCor Pharma Date: Jan. 9 Buyer: AstraZeneca Price: $1.8 billion AstraZeneca saw a good time to strike as CinCor Pharma's share price dropped throughout the winter of 2022. The U.K. pharma offered up $1.8 billion to bring on the blood-pressure-focused biotech, which is working toward a phase 3 study for aldosterone synthase inhibitor baxdrostat in uncontrolled hypertension. Story Blacksmith Medicines Date: Jan. 3 Buyer: Forge Therapeutics Price: N/A Blacksmith Medicines went back home in this transaction that saw the metalloenzymes-focused biotech spin right back into Forge Therapeutics. Blacksmith spun out of Forge in 2021. An entirely new entity, which the companies dubbed "the new Blacksmith," will emerge from the transaction to focus on oncology and infections. Story