Beta-Thalassemia

iStock, leolintang BioSpace has been compiling a list of the most innovative and exciting biotechs for a decade. Here we take a look back at noteworthy companies from each of those lists. 2024 marked the 10th year of BioSpace ’s NextGen list, a collection of biotechs that are on the cutting edge and poised to break barriers in the industry. As we prep next year’s list, to be released in January, we decided to take a look back at a notable honoree from each of our past lists. There were many fascinating companies that have gone on to great things; on the other hand, sometimes things don’t go as well as we predicted. We have a few not-so-great stories to tell, too. ___________________________________________ 2024 ReNAgade Therapeutics Status: Bought by Orna Therapeutics This company made our list for a pretty big reason: a massive $300 million series A in one of the toughest financing environments in recent memory. The company was launched in May 2023 to develop RNA medicines to treat diseases anywhere in the body. One of the lead investors in the round was MPM BioImpact, whose managing partner Ansbert Gadicke founded ReNAgade. Early in the biotech’s history as a stealth company, there was a bit of foreshadowing as to where the company would end up. ReNAgade struck up a partnership with Orna Therapeutics, which was also working on RNA therapeutics. The work attracted the attention of Merck in a deal worth up to $3.5 billion with development and commercialization milestones. Given the money on the line, Orna went all in on ReNAgade, buying out the biotech in May of this year—almost a year to the day after its launch. Financial details were not disclosed. See the full class of 2024 . ___________________________________________ 2023 Mariana Oncology Status: Bought by Novartis What a year 2023 turned out to be for Mariana Oncology. After raising a $175 million series B in September of that year, the company was bought out by Novartis for $1 billion , plus $750 million in milestones. Originally known as Curie Therapeutics, Mariana emerged from stealth with a $75 series A raise in December 2021 to develop new radiopharmaceuticals. The company caught our eye and made the 2023 list, but apparently Novartis was keeping an eye too. The radiopharmaceutical-hungry Big Pharma said at the time of the deal that Mariana’s technology would help it double down in the field of radioligand therapeutics. On a recent earnings call, Novartis executives expressed their excitement in the Mariana technology, saying that candidates from the buyout are speeding toward the clinic and could go after well-established antibody-drug conjugate (ADC) targets. See the full class of 2023 . ___________________________________________ 2022 Eikon Therapeutics Status: Operating Eikon has spent the two years since landing on our list racking up cash and poaching executives from CEO Rodger Perlmutter’s former employer Merck. The biotech’s raises have been huge in a really tough market: a $148 million series A in May 2021, $518 million for a January 2022 series B and most recently, $106 million in series C financing in June 2023 . At the most recent raise, Eikon also announced the acquisition of a clinical pipeline. The company now boasts oncology assets in Phase I and II testing for non-small cell lung cancer and melanoma, respectively. The rest of Eikon’s pipeline is in preclinical research or discovery. See the full class of 2022 . ___________________________________________ 2021 EQRx Status: Bought by Revolution Medicines, assets terminated EQRx emerged with a lofty goal we could all get behind: develop drugs at a lower cost. It raised a cool $200 million in a July 2020 series A, then caught the special purpose acquisition company (SPAC) wave to the Nasdaq just over a year later, adding $1.8 billion in an August 2021 IPO. The company was helmed at first by serial biotech entrepreneur Alexis Borisy. Trouble emerged shortly thereafter, with EQRx cutting lead asset sugemalimab for NSCLC after determining it had no path to market. The company shifted to two other assets, aumolertinib and lerociclib, but later dropped the former. Several rounds of layoffs made the company ever smaller before EQRx finally gave up entirely. The assets were terminated as Revolution Medicines bought out the company and its hefty $1 billion bank account. Borisy has since gone on to start a venture capital firm called Curie.Bio . See the full class of 2021 . ___________________________________________ 2020 Cerevel Therapeutics Status: Bought by AbbVie Cerevel as a company is no more, but its medicines live on at AbbVie, which bought the biotech for $8.7 billion in December 2023. The deal was part of a trend of neuroscience-focused biotechs being bought up by Big Pharma, with Cerevel moving in the same month as Bristol Myers Squibb bought Karuna Therapeutics for $14 billion. BMS was rewarded quickly with a recent FDA approval for KarXT (now Cobenfy) for schizophrenia, but AbbVie too has had success since sealing the deal. Cerevel’s investigational Parkinson’s disease therapy tavapadon improved control of motor symptoms when used with common treatment levodopa in a Phase III trial that read out in April. The data would support a regulatory filing for the therapy, executives said at the time. Two additional late-stage readouts for the therapy are due later this year. But the real star of the deal was emraclidine, which is in Phase III studies for schizophrenia. Cerevel also brought a major depression treatment to the table. “These assets clearly will be great additions to our neuroscience franchise,” said AbbVie’s CEO Rob Michael on the company’s second quarter earnings call. See the full class of 2020 . ___________________________________________ 2019 Genevant Status: Operating One of Roivant’s offshoots, Genevant is still operating today, working on developing nucleic acid delivery technology. Just last week, Genevant signed a deal with CRISPR gene editing company Editas Medicines to develop in vivo gene editing medicines for two undisclosed targets. Genevant has also recently signed deals with Novo Nordisk, Tome Biosciences, Gritstone bio and Repair Biotechnologies. But perhaps the most compelling story from Genevant since we named them to our NextGen list has been their litigation with famed biotech Moderna over the lipid nanoparticle delivery system used for its approved COVID-19 vaccine. Genevant and Arbutus Biopharma filed several patent infringement claims against Moderna arguing that the vaccine developer used their technology without license or proper compensation. A judge sided with Arbutus and Genevant in April, with a trial set for next year. See the full class of 2019 . ___________________________________________ 2018 BlueRock Therapeutics Status: Bought by Bayer Bayer bought cell therapy biotech BlueRock Therapeutics in August 2019 for $1 billion, but rather than absorbing the company into itself, the German pharma kept the name and unit operating. This unusual but refreshing strategy means that the company essentially lives on. In June 2023, BlueRock reported that Parkinson’s disease stem cell therapy bemdaneprocel was well tolerated with no significant side effects in a Phase I trial with 12 patients. It was the first cell therapy to show positive results in human testing, Bayer said at the time. A September update showed similar safety results. The therapy has since received a regenerative medicine advanced therapy tag from the FDA. Elsewhere in the pipeline, BlueRock’s investigational iPSC-derived cell therapy OpCT-001 for certain retinal disorders was cleared for human testing in September. The therapy was licensed from FUJIFILM Cellular Dynamics and Opsis Therapeutics. See the full class of 2018 . ___________________________________________ 2017 Decibel Therapeutics Status: Bought by Regeneron Regeneron made a splash at this year’s American Society of Gene and Cell Therapy meeting in Baltimore when it showcased results of a Phase I/II trial of hearing loss therapy DB-OTO. The therapy restored hearing in two children who had a genetic form of hearing loss. While Regeneron’s branding was behind the conference presentation, the gene therapy came from Decibel Therapeutics. Regeneron bought the biotech for $109 million in August 2023, at which point the two companies had already been working together for six years. The biotech was integrated into Regeneron’s genetic medicines portfolio. See the full class of 2017 . ___________________________________________ 2016 CRISPR Therapeutics Status: Operating CRISPR Therapeutics made history last year as the first company, along with partner Vertex Pharmaceuticals, to gain an FDA approval for a CRISPR-based gene edited therapy. The companies were granted an FDA greenlight for Casgevy in sickle cell disease. The same day, bluebird bio got a similar nod for a competing gene therapy, though not one that involves CRISPR technology. The FDA approval was a triumph of modern biotechnology. But the roll out has been slow given the nature of gene therapy treatment, and only recently have patients begun receiving infusions of the medicine. Casgevy is now also approved for beta thalassemia, another blood disorder. The company has turned to the rest of its pipeline, including a CD19-directed CAR T cell program called CTX112, which is being tested in both cancer and autoimmune disorders. CTX131 is in development for hematological malignancies as well. CEO Sam Kulkarni has expressed confidence in CRISPR’s leading position in gene editing and pledged to be on top of emerging technologies. “One of the most important considerations for us is that we don’t get disrupted,” he said at the Goldman Sachs healthcare conference in June. “We are the leaders in the gene editing space and we have been, but we want to make sure that we’re looking at every improvement that’s coming out there.” See the full class of 2016 . ___________________________________________ 2015 Spark Therapeutics Status: Bought by Roche Like BlueRock, Spark Therapeutics was folded into a Big Pharma but kept its identity. Spark earned a spot on our very first NextGen list in 2015 thanks to its active clinical hemophilia program and fundraises totaling $122.8 million. The company caught the eye of Roche, which swooped in with a $4.8 billion bid in February 2019. The deal eventually turned into a bit of a boondoggle, with regulatory delays slowing things down until it finally closed that December. At issue was Roche’s hemophilia Hemlibra. Regulators worried that Spark’s hemophilia program and Hemlibra together could stifle competition and create a monopoly. Spark brought with it the approved eye disease gene therapy Luxturna. With the deal closed, Spark has charged forward under the Roche banner. The unit is developing a 500,000-square foot Gene Therapy Innovation Center in Philadelphia as its flagship manufacturing space. See the full class of 2015 .

Clinical Trials at American Society of Nephrology (ASN) – Kidney Week 2024 SAN FRANCISCO, Oct. 28, 2024 /PRNewswire/ -- Kind Pharmaceutical ("Hangzhou Andao Pharmaceutical Ltd. and Kind Pharmaceuticals LLC"), a clinical-stage biopharmaceutical company focused on developing innovative medicines to treat hematological diseases and cancers, today announced that positive results of four clinical trials from its leading program AND017 to treat anemia in non-dialysis dependent chronic kidney disease (NDD-CKD) and dialysis-dependent chronic kidney disease (DD-CKD) were presented at annual meeting of American Society of Nephrology (ASN) Kidney Week in San Diego. The four clinical trials are first-in-human trial in healthy subjects in Austria (clinical trial "AU-001", NCT04751539), food effects on pharmacokinetics (PK) in China (clinical trial "CN-101", NCT04712500), phase 2 trial in anemia in NDD CKD in both US and China (clinical trial "MN-201", NCT05035641), and phase 2 trial in anemia in DD CKD in both US and China (clinical trial "MN-202", NCT05265325). In the AU-001 double-blinded, placebo-controlled, first-in-human clinical trial in healthy subjects in Australia, AND017 demonstrated favorable linear oral pharmacokinetics (PK) with T1/2 (elimination half-life) between 11.9 h and 19.7 h for the SAD part of trial (dosed from 1 mg to 50 mg) and T1/2 between 10.1 h and 19.4 h for the MAD part of trial (dosed from 4 mg to 30 mg QD for 10 days). In this trial, preliminary PD markers (EPO, Hb) were observed. In AU-001 trial, AND017 was safe and well tolerated in all doses (1 mg to 50 mg in SAD and 4 mg to 30 mg in MAD trials). In the CN-101 phase I, randomized, open-label, two-sequence, two-period, crossover, single dose (10 mg) trial, the effect of food on the PK of AND017 was studied in non-elderly healthy subjects in China. The Fed/Fasted ratio of geometric mean of Cmax was 79.61% with 90% CI (73.40, 86.34) and the Fed/Fasted ratio of geometric mean of AUC0-inf was 99.93% with 90% CI (96.31, 103,68). The CN-101 trial demonstrated that AND017 with the current formulation can be administered with or without food. In the MN-201 phase II, randomized, double-blinded, placebo-controlled, dose ranging study in U.S. and China, a total of 113 NDD CKD patients were randomized at 1:1:1:1 ratio to one of the four treatment groups to receive AND017 at three different doses of 8 mg, 12 mg, 16 mg, or placebo three times weekly (TIW) (28, 29, 28, and 28 patients respectively) in the first 5-week fixed-dose period; at Week 6 the drug-treated patients were combined and re-randomized to two TIW and once weekly (QW) dosing regimens to enter the 8-week titration period. At Week 6, the end of the titration period, all AND017 dose groups had significantly higher hemoglobin level (Hb) rise rate from baseline compared to placebo group; the dose of AND017 and the rate of rise in Hb were linearly correlated. After switching from the TIW dosing in the fixed-dose period, the Hb levels in both the TIW and QW dosing regimens maintained in the targeted range in the 8-week dose titration period. For the safety assessment, treatment emergent adverse events (TEAEs) occurred in 59 patients (69.4%) in the pooled AND017 group and 18 patients (64.3%) in the placebo group; the treatment-related TEAEs occurred in 10 patients (11.8%) in the pooled AND017 group and 1 patient (3.6%) in the placebo group. A total of six patients, three in AND017 12 mg group and three in AND017 16 mg group, experienced serious AEs (SAEs), none of which were assessed as treatment related. The MN-201 anemia in NDD-CKD trial demonstrated that AND017 was safe and well tolerated in NDD-CKD patients with safety prolife similar to the placebo; the drug effectively increased the Hb level in a dose-dependent manner starting at 8 mg TIW within the first 5-week fixed-dose period. The Hb levels were maintained within the target range 10.0-11.0 g/dL at both TIW and QW dosing groups in the following 8-week titration period. The MN-202 trial is a phase II, randomized, open-label, active-controlled study to treat anemia in patients with dialysis-dependent with end-stage kidney disease (ESKD) in both U.S. and China. Eligible patients were randomized at a ratio of 1:1:1 to AND017 10 mg TIW group (59 pts), AND017 16 mg QW group (56 pts), and the active comparator erythropoietin stimulating agents (ESA) group (59 pts) and patients were treated for a total of 20-week study treatment with doses of AND017 adjusted based on the study protocol and doses of ESA adjusted based on the local package insert or clinical practice to target Hb ranges within 11.0-11.0 g/dL in U.S. and 10.0-12.0 g/dL in China. In the primary efficacy analysis, both AND017 10 mg TIW and 16 mg QW groups showed non-inferiority to ESA in the maintaining Hb levels within the target range during the 20-week treatment. For the safety assessment, treatment emergent adverse events (TEAEs) occurred in 91 patients (78.4%) treated with AND017 and 39 patients (66.1%) treated with ESA. Among all frequently reported TREAEs, the only TEAE deemed treatment-related was hyperkalemia (1 patient, 1.7% from the AND017 10 mg TIW group); other treatment-related TEAEs were all <5% and occurred in no more than 2 patients in the pooled AND017 or ESA groups. A total of 48 patients experienced SAEs, with 35 patients (30.2%) treated with AND017 and 13 patients (22.0%) treated with ESA; none were assessed as treatment related. Both TIW and QW dosing regimens of AND017 effectively maintained Hb levels after 20 weeks of treatment in ESA-treated dialysis-dependent ESKD patients and demonstrated non-inferiority to ESA treatment with a favorable safety profile. "AND017 demonstrated adequate safety and effectively increased and maintained hemoglobin levels in the 10.0-11.0 g/dL range in two Phase II studies involving both NDD and DD CKD patient populations. Efficacy and safety will be further assessed in Phase III trials," said Pablo E. Pergola, MD, Ph.D., an expert in nephrology and the director of the Clinical Advancement Center, PLLC, a wholly-owned subsidiary of Renal Associates. "We are excited about the overall PK, efficacy and safety profiles of our compound; our results provided a once weekly, longer interval dosing option in the same class of drugs," Qi Zhu, MD, the CMO of Kind Pharmaceutical. "The longer interval dosing could be one of the keys to mitigate MACE issue, which plagued the previous clinical trials for anemia in NDD CKD. We are willing to tackle this tough problem in phase III trials." The summary of the results from the four clinical trials presented at ANS is shown below; for more detail, please read the posters from Kind's website. Last week FDA granted Orphan Drug Designation to this investigation drug in Sickle Cell Disease (SCD) treatment. About Anemia in Chronic Kidney Disease Chronic kidney disease (CKD) is very common in general population; the prevalence for CKD in the United States is about 14% in adults and that in China is about 8%. Anemia is a common complication in chronic kidney disease. There are about half million dialysis-dependent CKD anemia patients and about five million non-dialysis-dependent CKD anemia patients in US; it is estimated there are about 700K DD CKD anemia patients and about 50 million NDD CKD anemia patients in China. Anemia in CKD can increase the risk of cardiovascular complications, such as heart failure and stroke, and increase morbidity and mortality. About AND017 AND017 is a first-in-class hemoglobin elevating agent (HbEA) that targets multiple stages of the red blood cell (RBC) life cycle and is being developed to treat anemia associated with dialysis-dependent chronic kidney disease (DD-CKD), non-dialysis dependent chronic kidney disease (NDD-CKD), cancer-related anemia (CRA), myelodysplastic syndromes (MDS) anemia, sickle cell disease (SCD), and β-thalassemia. About Kind Pharmaceutical ("Hangzhou Andao Pharmaceutical Ltd. and Kind Pharmaceuticals LLC") KIND is a clinical-stage biopharmaceutical company focused on developing innovative medicines to treat hematological diseases and cancers. The company's mission, "kind to human, humble to science, good to patients", drives its commitment to advancing current science to meet unmet medical need. KIND's lead clinical candidate, AND017, first-in-class hemoglobin elevating agent (HbEA), is being developed for treating anemia of various disorders, including dialysis dependent chronic kidney disease (DD-CKD) associated anemia, non-dialysis dependent (NDD) CKD associated anemia, cancer related anemia (CRA), myelodysplastic syndromes (MDS) anemia, sickle cell disease (SCD), and β-thalassemia. KIND's second clinical candidate, AND019, an orally available brain penetrant selective estrogen receptor degrader (SERD), is being developed to treat ER+/Her2- breast cancer. KIND is also developing promising disruptive next generation ADC technologies. For details, please visit . Contact: Dong Liu, PhD, Chairman and CEO of Kind Pharmaceutical Email: [email protected] Tel: 650-315 6151 SOURCE Kind Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Sen. Tim Scott (R-SC) and Rep. Danny Davis (D-IL) are questioning the FDA’s “narrow” interpretation of “active ingredient” when it comes to awarding the potentially lucrative priority review vouchers. The letter , dated last Thursday and addressed to FDA Commissioner Rob Califf, focuses on the two FDA approvals of sickle cell gene therapies in late 2023. It explains how FDA’s recent administration of the PRV program — granting a PRV to one of the sickle cell gene therapies but not the other — “may not be fulfilling the program’s promise, original vision, and intent.” Scott and Davis question FDA on why it “made an initial decision to narrowly interpret the definition of ‘active ingredient’ in the PRV statute, resulting in the unexpected denial of at least one pediatric PRV.” But they also note that FDA “may be in the process of reconsidering its interpretation” so they want to make their thoughts clear. Bluebird bio had initially expected to win a PRV for its sickle cell gene therapy, approved in December 2023, and Novartis even drew up plans to purchase the PRV for $103 million. Ultimately, the FDA did not grant the PRV to bluebird, but Vertex Pharmaceuticals won a PRV for its gene therapy for sickle cell, approved on the same day as bluebird’s. A spokesperson told Endpoints News, “We believe that both the science and the congressional intent of the Rare Pediatric Disease Priority Review Voucher Program clearly support the issuance of a PRV associated with the approval of LYFGENIA and have continued to pursue a resolution with the FDA.” The FDA previously said that Lyfgenia contains the same active ingredient as bluebird’s gene therapy Zynteglo, approved for beta thalassemia. Scott and Davis explain how Congress did not define the term “active ingredient” in the law governing PRVs, but sought to prevent potential manufacturers from receiving PRVs for “simply making small tweaks to old drugs.” “The development of these complex gene therapies to treat an entirely new disease affecting thousands of patients can hardly be considered a ‘small tweak’ to an ‘old drug,'” the letter says, noting that Congress did not specify how FDA should determine if two active ingredients in an ex vivo gene therapy are the same or different. Scott and Davis add that FDA’s decision to interpret the law “in a narrower way than the statute requires – and one that flies directly against Congressional intent” risks disrupting “this delicate ecosystem, jeopardizing not only the availability of SCD treatments today, but also investments in complex and life-saving innovation for the future.” Editor’s note: Article updated with bluebird bio comment.