EVO-756

Today, a brief rundown of news involving Karyopharm Therapeutics and Amgen, as well as updates from BridgeBio Oncology Therapeutics, Evommune, Encoded Therapeutics and Schrdinger that you may have missed.Cash-strapped Karyopharm Therapeutics has reached a deal with creditors thatll give the company extra time to make a $15.8 million debt payment that came due on Thursday. According to a regulatory filing, a group of lenders, noteholders and royalty investors will hold off on taking action through Oct. 15, giving Karyopharm a little over a month to negotiate, pursue strategic alternatives or find additional financing. Karyopharm agreed to pay a $20 million fee in the form of newly issued convertible stock as part of the deal. Though lengthier financial relief wouldve been most ideal, the agreement at least buys the company time, wrote RBC Capital Markets analyst Brian Abrahams. Karyopharm is waiting to see whether U.S. regulators will accept an approval application for its multiple myeloma drug Xpovio in myelofibrosis. Ben FidlerA combination of Amgens Imdelltra and AstraZenecas Imfinzi helped people with first-line, extensive small-cell lung cancer live longer than Imfinzi alone in a Phase 3 trial. Amgen didnt provide specifics in a Tuesday statement, but said a trial monitoring committee detected a survival benefit among Imdelltra-Imfinzi recipients at an early data check, along with statistically significant improvements on measures of tumor progression and drug responses. Imdelltra is currently approved as a single agent for people whose disease gets worse following chemotherapy, and generated about $627 million in sales last year. Approval in the first-line setting could yield a significant expansion of the drugs sales potential, wrote William Blair analyst Myles Minter. Amgen will discuss the data with regulators.Jonathan GardnerEvommunes experimental drug EVO756 missed the main goal of a Phase 2 trial in atopic dermatitis, failing to significantly reduce the size or severity of skin lesions in atopic dermatitis patients when compared to a placebo, the company said Tuesday. The setback marks the second recent negative readout for EVO756, which fell short in a trial in chronic spontaneous urticariain June. Evommune has lost more than 40% of its market value since going public last year.EVO756s struggles have led investors to shift their attention to another therapy, EVO301, thats also in testing for atopic dermatitis, wrote Oppenheimer analyst Kostas Biliouris. That treatment looks interesting, as it might help people who dont respond to Dupixent, he wrote.Jonathan GardnerShares of BridgeBio Oncology Therapeutics have fallen by more than one-third since the company announced Tuesday its scaling back development for two KRAS-blocking drugs. BridgeBio dropped plans to test one drug, BBO-8520, in the first-line non-small cell lung cancer. It also deprioritized a breast cancer trial for a second therapy known as BBO-10203.BridgeBio made those decisions to focus resources on studies with the highest probability of success and greatest potential benefit for patients, among them a combination trial in second-line lung cancer. While those moves were prudent financially, they nonetheless eliminated a large potential opportunity, wrote Leerink Partners analyst Andrew Berens.Jonathan GardnerEncoded Therapeutics has raised a $275 million Series F round to advance a pair of gene therapies for neurological disorders, the company said. Encodeds most advanced candidate, a gene therapy dubbed ETX-101, showed in an early-stage trial the potential to lower the frequency of seizures and improve cognition in children with the rare genetic condition Dravet syndrome. A second program called ETX-301is in preclinical development for chronic pain from post-amputation neuromas, a thickening of nerve tissue that occurs after limb loss. Led by investors including GV, Arch Venture Partners and RTW Investments, the funding will also help Encoded boost its manufacturing capabilities. Gwendolyn Wu A biotech startup launched Wednesday bySchrdinger, RA Capital and New Enterprise Associates is setting out with a goal to develop drugs for inflammatory diseases. Called Tectora Therapeutics, the young company is starting up with $55 million to take forward two Schrdinger small molecules, called SDGR-4594 and SDGR-8139, into human testing.Multiple startups linked to Schrdinger have signed large deals with drugmakers, among them Nimbus Therapeutics, Morphic Therapeuticand Ajax Therapeutics.Nimbus sold some drug programs to Gilead Sciences and Takeda, while Morphic and Ajax were acquired by Eli Lilly. Gwendolyn Wu '

After flunking a mid-stage chronic spontaneous urticaria study in June, Evommune's oral MRGPRX2 antagonist, EVO756, suffered yet another setback — this time failing to clear a Phase IIb trial in moderate-to-severe atopic dermatitis (AD). Reacting to the news, the company's shares cratered nearly 27% in after-hours trading on Tuesday.With EVO756's urticaria programme already discontinued, Evommune has now decided to end AD development as well, leaving the drug’s remaining hopes pinned on its migraine indication. A mid-stage migraine prophylaxis study is currently underway.The AD trial randomised 121 adults to receive one of three EVO756 doses or placebo over a 12-week treatment period. Top-line results showed the trial failed to meet its main efficacy goal, with neither dose of EVO756 demonstrating a significant percentage change in Eczema Area and Severity Index (EASI) score from baseline at week 12. The study also fell short on secondary endpoints.HC Wainwright analysts earlier said that the company considered a profile similar to Galderma's Nemluvio (nemolizumab) — roughly 15% placebo-adjusted EASI improvement alongside meaningful itch relief — potentially adequate for an oral therapy, with greater lesion efficacy expected to widen its positioning."We are disappointed that this trial… did not meet its primary endpoint, particularly given the need for new treatment options for patients suffering from AD," said Eugene Bauer, chief medical officer of Evommune, noting that EVO756's favourable safety and tolerability, however, supported "its continued evaluation in migraine prophylaxis."Evommune, meanwhile, is strongly banking on its long-acting injectable SAFA-IL-18BP fusion protein EVO301 in AD, which delivered a positive Phase IIa readout in February, demonstrating efficacy comparable with Sanofi and Regeneron's Dupixent (dupilumab) and Eli Lilly's Ebglyss (lebrikizumab). A Phase IIb study is expected to commence mid-next year. (For more, read KOL Views Q&A: Evommune faces uphill battle in atopic dermatitis but there may be role for upstarts – one in particular).The biotech landed a $150-million IPO last November and went on to raise an additional $125 million in a private placement this year after EVO301's success. It maintains an operational runway through 2029.