PN-235

Several of Bristol Myers' top growth drivers face current and future challenges, according to the team at Leerink Partners. Several challenges across Bristol Myers Squibb’s business have Leerink Partners analysts worried about the future—despite a few promising growth opportunities the team has identified. A Leerink team led by David Risinger has lowered its revenue forecast for several important BMS growth products from 2025 and beyond. The TYK2 anti-inflammation drug Sotyktu, the S1P receptor modulator Zeposia, the multiple myeloma CAR-T Abecma, the immunotherapy fixed combo Opdualag, and the newly acquired antipsychotic candidate KarXT each face their own challenges, the team said. In addition, industry watchers will have a better idea on the price-reduction impact of the Inflation Reduction Act for BMS’ Pfizer-partnered megablockbuster blood thinner Eliquis later this year. With Revlimid losing market exclusivity and Opdivo facing patent expirations later this decade, BMS is fully aware it’s heading into a transition period. But it has been counting on its newer meds to drive “top-tier” growth from late 2020s, executives have said. For Sotyktu, a first-in-class pill that’s approved for plaque psoriasis, the Leerink analysts flagged “severe payer access restrictions,” as well as potential launches of rival oral agents in 2027 and beyond. Under continued pricing pressure, BMS anticipates only 10% sequential revenue growth for Sotyktu in the second quarter of this year, a relatively modest figure for a new launch. “As we see it, the company effectively has to give Sotyktu away (for just the copay card $ amount it receives from patients) until it can generate enough volume to justify being covered by formularies,” the Leerink team said in a Friday note. BMS doesn’t have much time to make it worthwhile for payers. Johnson & Johnson is running the phase 3 ICONIC-ADVANCE 2 trial pitting its novel oral IL-23R antagonist, JNJ-2113, against Sotyktu in plaque psoriasis. The trial bears a primary completion date in February 2025. BMS has labeled Sotyktu as a “key growth driver to establish leadership in immunology.” The drug is looking at a potential phase 3 readout this year in psoriatic arthritis, plus other expansion opportunities in autoimmune diseases such as lupus and Sjogren’s syndrome down the line. But Leerink has now pegged Sotyku to reach estimated 2030 sales of just $832 million, way below the $1.9 billion Wall Street consensus. BMS’ own projection? More than $4 billion in peak sales. Also in BMS’ immunology franchise, a phase 3 failure in Crohn’s disease was a clear blow to Zeposia, especially as AbbVie’s oral JAK inhibitor Rinvoq and injectable Skyrizi each chalked up wins in the inflammatory bowel disease subtype. In Leerink’s updated calculation, Zeposia is expected to reach worldwide sales of $805 million in 2030. BMS, for its part, has estimated the drug could bring in $3 billion by that time. One possible bright spot in BMS’ immunology franchise comes in the form of a CAR-T program, CD19 NEX-T, for lupus. Recent anecdotal reports of remarkable results in serious lupus cases have triggered enthusiasm for using CAR-T cells to eliminate autoreactive B cells behind the disease—perhaps for good. But a case of fast relapse despite initial response from Kyverna Therapeutics’ CAR-T candidate in lupus nephritis has cast a shadow over the strategy. BMS is expected to report phase 1 data for NEX-T later this year, the Leerink team noted. Speaking of CAR-T, BMS has been struggling with its anti-BCMA therapy Abecma because of tough competition from Johnson & Johnson and Legend Biotech’s Carvykti. With a recent FDA approval, Carvykti has jumped into the second-line treatment setting, whereas Abecma has only reached the third line. In addition, Carvykti’s new overall survival win will likely put it even further ahead of Abecma in doctors’ minds. During an investor call in March, Legend execs noted that Carvykti was holding about 80% of market share at treatment centers that offer both BCMA CAR-Ts. Legend execs said the company was looking to snatch the remaining share by increasing supply, arguing that BMS’ Abecma was only able to secure its own share thanks to Carvykti’s production bottleneck. Leerink now projects Abecma sales of just $556 million in 2030. Both Wall Street consensus and Bristol’s own target have put the number at above $1 billion. Prospects are not that sunny elsewhere on BMS’ home turf of oncology. Specifically, the PD-1/LAG-3 combo Opdualag may “face serious competition” from Regeneron’s LAG-3 candidate fianlimab, the Leerink team pointed out. Fianlimab’s phase 3 data in first-line melanoma are expected in 2025, and Regeneron has been bullish that its data will look better than Opdualag in a cross-trial comparison, the Leerink analysts said. The more important indication for the checkpoint inhibitor class is lung cancer. There, BMS’ chief medical officer, Samit Hirawat, M.D., recently told Leerink analysts that Opdualag has shown positive phase 2 data in an undisclosed subset of non-small cell lung cancer patients, who represent about 20% to 30% of the patient population. A phase 3 trial in that subgroup is being planned for the second half of this year. BMS’ plan was to advance the combination of Opdualag and chemotherapy and compare it against Keytruda and chemo. But the company would need to discuss the control arm comparator with the FDA given the evolving treatment landscape, the Leerink team said in a note in March. Should a newer treatment regimen be included for comparison, BMS may have to face a higher efficacy bar than it had encountered in the phase 2, the Leerink analysts said. Elsewhere, BMS recently acquired Karuna and its close-to-market schizophrenia candidate KarXT in a $14 billion deal. The New Jersey pharma has touted the drug’s “multibillion-dollar” peak sales potential if future clinical studies pan out. With an FDA target date in September, BMS plans to launch the first-in-class M1/M4-preferring muscarinic agonist this year. But Leerink learned that BMS’ filing in Europe has to wait for data readouts from head-to-head trials against generic drugs because EU government payers will only cover KarXT if it shows superior benefit to readily available meds. As a result, Leerink has lowered KarXT’s ex-U.S. sales estimates. Still, the team’s global 2030 sales projection for KarXT in schizophrenia, at $3.6 billion, is above the consensus figure of $3.1 billion. In Alzheimer’s disease psychosis, Leerink expects potential sales of $916 million, compared with $843 million for consensus. BMS faces all these challenges while dealing with mandated price adjustments for Eliquis as one of the first 10 drugs selected for Medicare price negotiations under the IRA. The U.S. government will publish the maximum prices negotiated for those drugs by September 1, and BMS will provide guidance on the impact on Eliquis after that. The prices will go into effect in 2026.

Long term follow-up from REVIVE Phase 2 study up to 3 years shows durable hematocrit (Hct) control (< 45%), decreased phlebotomy use, long-term tolerability, and no new safety signals in patients with polycythemia vera Patients receiving rusfertide in the open-label extension of the REVIVE study are eligible to roll over to the THRIVE study for an additional 2 years of treatment NEWARK, CA / ACCESSWIRE / June 14, 2024 / Protagonist Therapeutics, Inc. ("Protagonist" or the "Company") announced details from two abstracts at the European Hematology Association 2024 Congress, including an oral presentation with long-term follow-up data from the Phase 2 REVIVE study with rusfertide, a mimetic of the natural hormone hepcidin with potential therapeutic value in the treatment of polycythemia vera (PV) and other disease indications. Copies of the presentations will be available on the Events and Presentations section of the Protagonist website. Kristen M. Pettit, M.D., Clinical Associate Professor at University of Michigan Health presented the long-term follow-up data from patients in REVIVE who continued into the open label extension (OLE). The Phase 2 trial consisted of 3 parts including 70 patients in the dose-finding Part 1 (28 weeks), 59 patients in the placebo-controlled, randomized withdrawal Part 2 (13 weeks), and 58 patients in the Part 3 OLE (52 weeks). The THRIVE study provides OLE for an additional two years of treatment to patients who have completed Part 3 OLE of the Phase 2 REVIVE study. As of April 9, 2024 (data cut-off for the EHA presentation), 47 patients (81.0%) remain on rusfertide, with 48 patients treated for two or more years and 10 patients treated for three or more years. Of the 58 patients who entered the REVIVE Part 3 OLE, the median duration of therapy is 124.3 weeks as of the April 9, 2024 data cut-off, and 24 patients have rolled over to the THRIVE study for up to two additional years of rusfertide treatment. "These long-term REVIVE data continue to showcase the positive clinical impact that rusfertide has on PV patients," noted Dr. Kristen M. Pettit. "With up to three years of data showing strong and lasting improvements in hematocrit as well as previous evidence of symptom improvement, rusfertide continues to demonstrate its potential as an important future treatment option for patients with polycythemia vera." The updated long-term data showed that rusfertide when added to therapeutic phlebotomy with or without cytoreductive therapy resulted in: Long term durable control of hematocrit below the 45% threshold for up to 3 years Decreased phlebotomy use, from a rate of 8.7 per year before study entry to 0.43 per year in Part 3 of REVIVE, which remained consistent with the rate of 0.36 per year observed for patients randomized to rusfertide in Part 2 of REVIVE Decreased red blood cell counts and continued improvement and normalization of serum ferritin levels Mean leukocyte counts remained stable throughout the study; an asymptomatic increase in platelets was observed with initiation of rusfertide treatment but stabilized over time No new safety signals with the majority of adverse events being Grade 1-2 injection site reactions or adverse events consistent with the comorbidities commonly associated with polycythemia vera In REVIVE, 19 of 70 patients (27.1%) had a history of cancer prior to enrolling in the study. Among these, 10 (14.3%) had a history of skin cancer. As of April 9, 2024, there are 11 patients diagnosed with malignancies while on study (11/70; 15.7%), including 9 with skin cancer (9/70; 12.9%). All cancers occurred in patients with risk factors such as a prior history of cancer, previous cytoreductive therapy, pre-existing skin lesions that were not biopsied or photosensitive skin. All skin cancers were localized, early stage (in situ or stage 1) and all patients remained on rusfertide after the skin lesions were excised. "The long-term open label rusfertide data from REVIVE study continue to show a durable positive effect on PV symptomology and other benefits including iron deficiency as well as a solid safety profile. Patients completing the 3-year open-label extension can roll over to the THRIVE open-label study for an additional 2-years providing efficacy and safety for a total of up to 5.8 years of rusfertide treatment," said Arturo Molina, M.D., M.S., Chief Medical Officer of Protagonist. "We are very pleased with the continued favorable safety pro look forward to the top-line data for the VERIFY Phase 3 study's 32-week primary efficacy endpoint by the end of the first quarter of 2025." A separate abstract accepted for publication only was titled "Absence of QTC Prolongation with Rusfertide, a Hepcidin Mimetic for the Treatment of Polycythemia Vera: A Thorough QT/QTC Study in Healthy Subjects." In this study, 60 healthy subjects were randomized to receive single doses of subcutaneous rusfertide (90mg), matching placebo, or oral moxifloxacin (400mg).Rusfertide was generally well tolerated and did not result in a clinically relevant prolongation of the QTcF interval. About Protagonist Protagonist Therapeutics is a biopharmaceutical company with peptide-based new chemical entities (NCEs) rusfertide and JNJ-2113 (formerly PN-235) in advanced stages of clinical development, both derived from the Company's proprietary technology platform. Protagonist and JNJ scientists jointly discovered PN-235 (now known as JNJ-2113) as part of Protagonist's Interleukin-23 receptor (IL-23R) collaboration with JNJ and followed it through IND-enabling pre-clinical and Phase 1 studies, with JNJ assuming responsibility for further clinical development. Rusfertide, a mimetic of the natural hormone hepcidin, is the Company's lead drug candidate currently in a global Phase 3 development program. The randomized portion of the Phase 2 REVIVE study was unblinded, showing positive results and is now complete, with an open-label extension underway. The global Phase 3 VERIFY study of rusfertide in polycythemia vera is ongoing. Rusfertide will be co-developed and co-commercialized with Takeda pursuant to a worldwide collaboration and license agreement with Takeda entered into in January 2024 and became effective in March 2024. More information on Protagonist, its pipeline drug candidates and clinical studies can be found on the Company's website at . Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include statements regarding the potential benefits of rusfertide. In some cases, you can identify these statements by forward-looking words such as "anticipate," "believe," "may," "will," "expect," or the negative or plural of these words or similar expressions. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, our ability to develop and commercialize our product candidates, our ability to earn milestone payments under our collaboration agreement with Janssen, our ability to use and expand our programs to build a pipeline of product candidates, our ability to obtain and maintain regulatory approval of our product candidates, our ability to operate in a competitive industry and compete successfully against competitors that have greater resources than we do, and our ability to obtain and adequately protect intellectual property rights for our product candidates. Additional information concerning these and other risk factors affecting our business can be found in our periodic filings with the Securities and Exchange Commission, including under the heading "Risk Factors" contained in our most recently filed periodic reports on Form 10-K and Form 10-Q filed with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements, whether as a result of new information, future events or otherwise, after the date of this press release. Investor Relations Contact Corey Davis, Ph.D. LifeSci Advisors +1 212 915 2577 cdavis@lifesciadvisors.com Media Relations Contact Virginia Amann ENTENTE Network of Companies virginiaamann@ententeinc.com +1 833 500 0061 SOURCE: Protagonist Therapeutics, Inc. View the original press release on accesswire.com