Pathalys Pharma, Inc.

A team that got a gout treatment approved is coming back together to develop a new medicine for the condition in the US and Europe. Crystalys Therapeutics, the San Diego biotech developing the oral gout drug dotinurad, emerged on Tuesday with $205 million in Series A funds. The company previously raised $23 million in seed funds, CEO James Mackay told Endpoints News. The startup began two Phase 3 trials last month, Mackay said , and the company should have results from the pivotal studies at the end of 2027. Mackay formerly led AstraZeneca’s Ardea Biosciences, which developed a gout drug called Zurampic that received a green light from the FDA in 2015. Crystalys could be a “nice bolt-on acquisition” for a pharma company with interest in rheumatology or I&I, but “that’s not something we’re planning on,” according to Mackay. The company is prepared to take dotinurad all the way to market on its own, he said. The launch of Crystalys is part of an increasingly common trend among biotech investors. They acquire or in-license a clinical-stage drug candidate, build a company around it, stack the C-suite with industry veterans, and then commit a heap of capital for human trials. This time, the acquired asset is already on the market in a handful of countries. Fuji Yakuhin developed dotinurad, which was approved to treat gout in Japan in 2020. Then in December, Eisai secured a regulatory nod in China for the same drug, launching the medicine there this summer as Urece . It’s also greenlit in Thailand and the Philippines. Crystalys has the rights to dotinurad in the US, Europe, North Africa and Middle East after the company licensed dotinurad from Fortress Biotech subsidiary Urica Therapeutics in July 2024. Urica had the license from Fuji Yakuhin. Mackay said the funding should carry the company through the Phase 3 readouts and some small Phase 2 life cycle management studies that it’s still mapping out, Mackay said. After his time at AstraZeneca, Mackay went on to found and lead an inflammatory disease biotech called Aristea Therapeutics, which shut down in early 2023 after safety concerns in clinical studies. Not long after, executives at Aristea’s lead investor Novo Holdings told Mackay that they were “really interested in getting into the gout space,” he said. The team wanted him to start a gout-focused biotech given his experience leading AstraZeneca’s gout work. With the help of Novo Holdings and Catalys Pacific, a biotech fund in Tokyo and Seattle, they conducted a “landscape search of all the gout drugs in development” and evaluated seven or eight molecules before choosing dotinurad, according to Mackay. Crystalys was then able to bring in more investors. Along with Novo Holdings and Catalys, its investors are SR One, Perceptive Xontogeny, Lightstone, AN Venture Partners and more than half a dozen other firms. Catalys founder BT Slingsby serves as board chair. He has co-founded companies like hypertension biotech Mineralys Therapeutics and chronic kidney disease drug developer Pathalys Pharma. In a press release, Slingsby noted “Japan’s excellence in pharmaceutical innovation.” Crystalys is evaluating dotinurad as a once-daily oral drug that inhibits the URAT1 protein, which acts as the “main renal transporter that basically moves uric acid in and out of the body,” Mackay said. Inhibiting that target should lead patients to urinate more uric acid out of their body and, in effect, address the root cause of gout, he said. Gout typically occurs when a patient’s body is unable to excrete enough uric acid. The condition leads to intense pain attacks and big lumps on the joints, which develop as uric acid builds up. It’s the most common type of inflammatory arthritis. The “beauty of dotinurad,” Mackay said, is that it’s already been given to about 1.2 million people in Japan, so there’s ample safety data and there has been “no significant change” in the label in Japan in five years. Crystalys’ experienced team, which includes chief medical officer Nihar Bhakta, wanted a drug that came with no renal toxicities or liabilities, according to Mackay. Dotinurad should be able to avoid those toxicities because it is “highly specific” to URAT1 and not other renal transporters, he said. The company hopes to give gout patients the option to take an oral treatment. Amgen markets an IV-delivered molecule called Krystexxa by way of its $28 billion Horizon acquisition. Zurampic was an oral drug, but it was discontinued after Ironwood terminated its licensing agreement with AstraZeneca in 2018. Like Horizon, Crystalys aims to market the drug as a specialty treatment prescribed by rheumatologists and not primary care physicians, Mackay said. “That makes it very achievable for us a relatively small biotech to launch the drug,” he added.

The FDA's approval for Yuhan's J&J-partnered Lazcluze, Merck and Kelun's revised ADC deal, and U.S. lawmakers' scrutiny of clinical trials run at Chinese military hospitals made our news this week. Yuhan's Lazcluze, licensed by Johnson & Johnson, has made history as the first Korea-developed novel cancer drug to be approved by the FDA. Merck has optioned in on one Kelun Biotech antibody-drug conjugate but returned another. A few U.S. lawmakers have asked the FDA to examine clinical trials involving sites at Chinese military hospitals. And more. 1. Targeting AZ's Tagrisso, Johnson & Johnson's Rybrevant combo wins key FDA nod in first-line lung cancerThe FDA has approved Johnson & Johnson’s Rybrevant and Lazcluze for newly diagnosed EGFR-mutant non-small cell lung cancer. The combo will compete with AstraZeneca’s Tagrisso. J&J in-licensed Lazcluze, a third-generation EGFR tyrosine kinase inhibitor, from Korea’s Yuhan in 2018. The drug is now the first Korea-developed novel anti-cancer therapy to be approved by the FDA.2. Merck & Co. bags one Kelun ADC for $37.5M, boots out another asset as pipeline tinkering continuesMerck and Kelun Biotech have reworked their multi-asset ADC deal. The New Jersey pharma has decided to return the CLDN18.2-directed SKB315. Although no reason was offered, the CLDN18.2 space has become very crowded with multiple firms exploring various modalities. Merck also agreed to pay $37.5 million to take up an option on a new candidate, a bispecific ADC coded SKB571, although the exact drug target remains unclear.3. Lawmakers urge FDA to investigate clinical trials run in tandem with China's militaryLawmakers on the House Select Committee on the CCP are asking the FDA to scrutinize clinical trials conducted at Chinese military hospitals. The lawmakers questioned the trustworthiness of data generated at those sites and potential risks for U.S. intellectual property. Trials of Eli Lilly’s Alzheimer’s disease drug Kisunla and Pfizer’s cancer med Inlyta were raised as examples. 4. Despite looming BIOSECURE threat, pharma contracting giant WuXi Bio scoops up new projectsMeanwhile, as the House is reportedly gearing up for a vote on the BIOSECURE Act in September, WuXi Biologics said it had added 61 new projects in the first six months of 2024, half of which came from the U.S. Fifty-two of the new projects are for preclinical candidates and five for early clinical work. The number of new projects compares favorably to the company’s haul during the same period last year.5. FDA allows BioNTech-MediLink ADC trial to resume with lower, safer dosesAfter a safety scare in mid-June, the FDA has allowed MediLink Therapeutics to restart a phase 1 trial of its BioNTech-partnered HER3-directed ADC. Before the halt, the trial had recorded three deaths across two dose cohorts. Now, BioNTech said it will focus solely on doses no higher than 3mg/kg as MediLink “had observed a dose level-dependent trend of treatment-related adverse events.”6. Denmark's Adcendo signs $1B biobuck deal for Multitude’s anti-TF ADCDenmark’s Adcendo has signed a $1 billion biobucks deal to get ex-China rights to a preclinical ADC from Sino-American biotech Multitude Therapeutics. The candidate, coded ADCE-T02, targets tissue factor. A phase 1 trial of the drug is scheduled to start in Australia in the fourth quarter, and Adcendo is planning to get FDA’s green light to launch a U.S. study “in the near future.”7. Eisai, Biogen's Leqembi nabs UK nod, but reimbursement remains elusiveThe U.K. has approved Eisai and Biogen’s Leqembi for early-stage Alzheimer’s disease but excluded patients with two copies of the ApoE4 gene out of safety concerns. Still, the National Institute for Health and Care Excellence has tentatively denied coverage of the drug under Britain’s taxpayer-funded insurance program. The drug cost watchdog cited Leqembi’s “relatively small benefits” and high costs.Other News of Note: 8. Astellas employee held in China indicted by China’s prosecutors9. Insulet unveils $200M insulin delivery device production site in Malaysia10. Pathalys raises $105M series B to prepare Japan-approved kidney disease drug for FDA11. FDA rebukes another troubled Eugia production site with a warning letter12. Korea’s Bridge Biotherapeutics, China’s HitGen sign drug discovery pact for cancer (release)13. Pfizer pulls smoking cessation drug Champix from Korean market (Korea Biomedical Review)

The approval of Dupert is grounded in the outcomes of a Phase II clinical study. Credit: mi_viri/Shutterstock. China’s National Medical Products Administration (NMPA) has granted approval for Innovent Biologics ’ Kristen rat sarcoma (KRAS) G12C inhibitor, Dupert (fulzerasib), to treat advanced non-small cell lung cancer (NSCLC) in adults. It is approved for NSCLC treatment in adults with the KRAS G12C mutation who have received a minimum of one systemic therapy. Dupert is orally administered and targets the guanosine triphosphate/guanosine diphosphate exchange process by covalently and irreversibly modifying the KRAS G12C protein’s cysteine residue. Preclinical studies have shown fulzerasib’s high selectivity towards G12C, effectively inhibiting downstream signalling pathways, leading to apoptosis [programmed cell death] and cell cycle arrest in tumour cells. The approval of Dupert is grounded in the outcomes of a Phase II clinical study, which assessed the efficacy and safety of fulzerasib monotherapy in Chinese patients with advanced NSCLC and the KRAS G12C mutation. See Also: Pathalys secures $105m to advance SHPT drug through approval FDA declines to approve Regeneron’s linvoseltamab amid manufacturing issues As of 13 December 2023, the study had enrolled 116 evaluable subjects, demonstrating that fulzerasib was generally well-tolerated and exhibited promising antitumour activity. The Independent Radiology Review Committee (IRRC) confirmed an objective response rate (ORR) of 49.1% and a disease control rate of 90.5%. The median duration of response and overall survival has not yet been reached, with a median progression-free survival of 9.7 months. In September 2021, Innovent entered an exclusive licence agreement with GenFleet Therapeutics for the development and commercialisation of fulzerasib in China, including mainland China, Hong Kong, Macau and Taiwan. The therapy has received breakthrough therapy designation (BTD) from the Center for Drug Evaluation (CDE) of China’s NMPA twice, first in January 2023 for advanced NSCLC and again in May 2023 for advanced colorectal cancer with the KRAS G12C mutation. Innovent senior vice-president Dr Hui Zhou stated: “Patients with advanced NSCLC harboring KRAS G12C mutations have limited treatment options, with traditional chemotherapy offering minimal benefits. “We are excited that Dupert has become the first KRAS G12C inhibitor approved in China, marking the beginning of a new era in targeted therapy for KRAS mutations. As Innovent’s eleventh drug, Dupert further strengthens our robust oncology portfolio.”