Pazopanib Hydrochloride

Hereditary hemorrhagic telangiectasia is the second most common inherited bleeding disorder in the world and has been linked to severe disease burden, reduced life expectancy and a reduced quality of life. Vaderis Therapeutics’ goal to develop the first drug aimed specifically at a certain rare blood vessel disorder came one step closer today with the news that the therapy is safe and reduced nosebleeds.The therapy in question, a once-daily allosteric AKT inhibitor dubbed VAD044, was trialed in 75 patients with hereditary hemorrhagic telangiectasia (HHT), a genetic disorder that leads to abnormal blood vessels forming in the skin, mucous membranes and certain organs.Almost all HHT patients suffer from unpredictable and often debilitating nosebleeds. After 12 weeks, patients who received the 40-mg dose of VAD044 experienced “clinically meaningful” reductions in the frequency of their nosebleeds, a secondary endpoint of the trial, Vaderis said in an Aug. 27 release.The release was light on any actual data, but the Swiss company did say that regression of HHT-associated vascular lesions was also observed.Patients in the phase 1 trial either received the 40-mg dose, a 30-mg dose or placebo. The primary endpoint of the study was safety, and the data showed that VAD044 was similar to placebo when it came to the frequency and severity of off-target adverse events (AEs). On-target AEs associated with inhibiting the AKT pathway—which helps cells survive and grow in response to extracellular signals—were mostly mild, transient and resolved, the company said.Some of the patients have since been enrolled in a 12-month open-label extension, where they are receiving a 40-mg daily dose of VAD044. Interim six-month data from 27 of these patients “continue to show favorable safety and tolerability profiles with further improvements” in nosebleeds, Vaderis said.CEO Nicholas Benedict said the company is already “interacting with major health authorities to plan the pivotal phase of development for VAD044 in HHT.”“The excitement surrounding the results of the initial 12-week double-blind part of this trial is amplified by the continued improvements experienced by patients through six months,” Benedict added. HHT is the second most common inherited bleeding disorder in the world and has been linked to severe disease burden, reduced life expectancy and a reduced quality of life. Despite this health impact, there are no approved treatments for the condition, according to Vaderis, which described VAD044 as “the first novel therapy intended specifically for the treatment of HHT.”The company is also lining up the therapy to test in breast and prostate cancers, according to Vaderis’ website.“We … already see that after six months of continuous treatment with VAD044 patients experience further improvements in all [nose bleeding] endpoints compared to those seen at 12 weeks,” Hans-Jurgen Mager, M.D., Ph.D., head of the Netherlands Reference Centre for HHT and the study’s co-primary investigator, said in a statement.“It seems that VAD044 has not yet reached its peak effect on HHT disease activity at 12 weeks, and patients continue to improve over time without paying an unexpected price in terms of safety or tolerability,” Mager added.Academic centers in the U.S. are currently enrolling patients to test whether Novartis’ sarcoma drug Votrient can reduce the severity of nosebleeds in HHT. Votrient is a tyrosine kinase inhibitor that has been shown to inhibit the PI3K/Akt signaling pathway.Novartis has a more direct link to Vaderis, with the biotech having been set up in 2019 by two veterans of the Swiss Big Pharma, including Benedict himself.

UTRECHT, The Netherlands and CAMBRIDGE, Mass., June 02, 2024 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced updated interim clinical data on MCLA-145 monotherapy and in combination with pembrolizumab were presented at the 2024 American Society of Clinical Oncology® (ASCO®) Annual Meeting taking place in Chicago May 31-June 4, 2024. “MCLA-145 as monotherapy or with pembrolizumab appears to have a manageable safety profile and early clinical activity in these difficult to treat cancers. Our biomarker data suggest that both dose and less frequent administration may be important determinants of clinical activity, and we are encouraged by the progress we are making with MCLA-145,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “As our company is now increasingly focused on our lead asset petosemtamab and plan to initiate phase 3 trials in head and neck cancer later this year, we aim to advance clinical development of MCLA-145 in the context of a potential collaboration.” MCLA-145 (CD137 x PD-L1 Biclonics®): Solid Tumors Interim data included in the presentation describe data from patients (pts) with advanced/metastatic solid tumors who received MCLA-145 Q2W in 28 day cycles or every three weeks (Q3W) in 21 day cycles. Pts treated with the combination of MCLA-145 and pembrolizumab had cancers that either relapsed after PD-(L)1 therapies or were immunotherapy (IO) naïve. Rapid oral presentation title: Phase I study of MCLA-145, a bispecific antibody targeting CD137 and PD-L1, in solid tumors, as monotherapy or in combination with pembrolizumabObservations in the presentation include: As of a January 3, 2024 data cutoff date, 72 pts with multiple cancer types were treated; 25% of pts had non-small cell lung cancer (NSCLC) All patients were heavily pre-treated with a median of 3 prior therapies; prior IO in 49% of the monotherapy pts and 100% of the combination pts In monotherapy, 52 pts with a variety of tumor types and treated at different dose levels were evaluable for response 5 partial responses (PRs) were observed at different dose levels in glioblastoma (ongoing as of the cutoff date for >3 years), sarcoma (pretreated with pazopanib and gemcitabine/docetaxel), cervical, anal, and gastric cancer by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment2 of 6 pts PRs (33%) were observed for pts treated at the recommended dose for expansion (RDE), 40 mg Q3W3 of 6 PRs (50%) were observed for pts with evaluable baseline tumor CD8 T-cell density of ≥ 250 cells/mm2 responded In combination with pembrolizumab, 19 pts with a variety of tumor types and treated at different dose levels were evaluable for response 1 PR in Merkel cell carcinoma was observed at 25 mg Q3W1 complete response was observed in PD-L1+ NSCLC at the RDE 40 mg Q3W3 pts were continuing combination therapy at cutoff date MCLA-145 monotherapy or in combination with pembrolizumab had a well-tolerated and manageable safety profile at the RDE, 40mg Q3W Shifting from Q2W to Q3W resulted in a 50% reduction of Grade (G) ≥3 treatment-emergent adverse events in both monotherapy and combination therapyLiver toxicity, a common CD137 related adverse event, was controlled with no G4 events observed at Q3W The full presentation is available on the Merus website. About MerusMerus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, X and LinkedIn. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the clinical development of our clinical candidates, including MCLA-145, future clinical trial results or interim data, clinical activity and safety profile, and development plans in the on-going trials and described in forthcoming posters or presentations; the ability of our Mutliclonics®; our belief that for MCLA-145, biomarker data suggest that both dose and less frequent administration may be important determinants of clinical activity; our statements concerning the progress we are making with MCLA-145; our increasingly focus on our lead asset petosemtamab and plan to initiate phase 3 trials in head and neck cancer later this year; and our aim to advance clinical development of MCLA-145 in the context of a potential collaboration. These forward-looking statements are based on management’s current expectations. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or Biclonics®, Triclonics® and multispecific antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the market volatility; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. These and other important factors discussed under the caption “Risk Factors” in our Annual Report on Form 10-Q for the quarter ended March 31, 2024 filed with the Securities and Exchange Commission, or SEC, on May 8, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. Multiclonics®, Biclonics® and Triclonics® are registered trademarks of Merus N.V.