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Ligand Pharmaceuticals Incorporated (LGND)

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124.91-0.42 (-0.34%)
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124.91 0.00 (0.00%)
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  • l
    longvrts
    From JP Morgan day 2 (courtesy of biopharma dive): the featured oncology immunotherapeutics are... drumroll please...OmniAb based Sugemalimab and Tiragolumab! Tiragolumab is first-in-class and best-in-class anti-TIGIT mAb being developed by Roche (Roche bought out the royalties early on, so only potential milestones to LGND on this mAb). Sugemalimab is licensed to CStone Pharma in greater China- where it already received marketing approval- and by EQRx in US+EU+ROW. LGND will receive milestones and royalties on global Suge sales:

    "Can Roche beat Merck and Bristol Myers?
    It's not a stretch to say Roche, the biggest cancer drugmaker in the world by sales, has been surpassed by some of its rivals in the fast-moving immunotherapy field. Revenue for its top cancer immunotherapy, Tecentriq, is dwarfed by the billions of dollars generated by Merck and Bristol Myers' similar medicines. Merck's Keytruda, in particular, has become a standard treatment in many tumor types.

    "We were really late to the game," Roche's Anderson conceded on Tuesday. But the company believes it will close the gap this year, thanks to the edge it currently has on others in developing a new type of immunotherapy aimed at the protein TIGIT.

    The drug, tiragolumab, is part of a group of TIGIT-blocking drugs from Merck, Bristol Myers, Gilead and several other companies. These medicines have become some of the most closely watched research programs in oncology, propelled by early results showing they may boost the effects of drugs like Tecentriq and Keytruda, which don't work for everyone.

    Data Roche presented from a small study in December showed a particularly significant survival benefit for advanced lung cancer patients whose tumors express high levels of the protein PD-L1, more than half of whom were alive at least three years after starting treatment. "That's phenomenal in lung cancer," he said.

    Though promising immunotherapy combinations have disappointed before, Roche is betting TIGIT will be different. The company has launched nine pivotal trials — four of which, in tumors of the lung, esophagus and cervix, should produce results this year.

    "We said there were going to be three waves" in cancer immunotherapy, Anderson said. And the third, built on immunotherapy combinations, has the "ability for us to reclaim a leadership position."

    A head-to-head study with big implications
    Merck's Keytruda was approved in the U.S. just over seven years ago. Since then, six other drugs that work like it have won FDA clearances and a seventh is currently under regulatory review.

    The drugs, known as checkpoint inhibitors and targeting proteins called PD-1 or PD-L1, have become widely used and changed how some cancers are treated. But very little is known about how they compare to one another in tumor types for which several are approved. That's mostly because their makers, as is typical in the industry, are reluctant to run head-to-head trials for fear their medicine may prove less effective.

    This has frustrated the FDA. "Sponsors making claims about developing 'a better' checkpoint inhibitor should directly compare their agent with those that are already approved; unfortunately, there is no evidence that such randomized trials are under way," Richard Pazdur, one of the agency's top cancer drug evaluators, wrote in a recent editorial.

    That may change soon. EQRx, a richly funded biotech with grand plans to change how drugmakers do business, plans to run a head-to-head study comparing a checkpoint inhibitor it licensed from China's CStone Pharmaceutical directly against approved PD-1 or PD-L1 blockers.

    The study will be randomized and span multiple trial sites, at least some of which will be based in the U.S., according to Melanie Nallicheri, EQRx's CEO. "This is additional evidence that we believe our health community wants to see," she said in a presentation Monday.

    Nellacheri offered few other details, but said EQRx would start the study this year. The results could be instructive and, if favoring EQRx's medicine, boost the company's plan to challenge market incumbents. "
  • l
    longvrts
    Recent pps action: I see 3 things converging which have allowed the usual- and unfortunately cyclically repeating- short attack against LGND:

    1) sector rotation out of biotech and hitech into dividend paying blue chips.
    2) no announcement on CE-iohexol.
    3) pre-earnings quiet period.

    LGND hit $275/sh in 2018 on the strength of one asset, Promacta. Compare with today's status of LGND assets:
    - 31 marketed/"approved for marketing" assets.
    - OmniAb spin off (OmniAb's in 50 clinical trials, 80 programs currently).
    - Billion $ drug : Kyprolis and Remdesivir.
    - Marketing roll outs: Vaxneuvance, Rylaze, Sugemalimab, Zimberelimab.
    - on deck: Teclistamab, Tiragolumab, Sutimlimab, Sparsentan, CE-Iohexol, Ensifentrine, Reproxalap, Batoclimab, Pevonedistat.
    - Captisol

    If still waivering, meditate on the impact of 80 OmniAb programs and 50 OmniAb clinical trials (completed or underway)...and more to come!
  • A
    Anonymous
    Only short term problem I see is the big recent drop in Ligand partner VKTX. LGND owns 5.8 million shares and that will be reflected in4th quarter earnings.
    Anyone have opinion on 2B Nash trial for VKTX?
  • l
    longvrts
    Sparsentan news: Travere Therapeutics announces update on Sparsentan. NDA will be submitted for IgA nephropathy indication in 1Q'21 and under accelerated approval process FDA marketing authorization expected by YE'21. LGND will receive milestones and royalties of 9% on global sales of Sparsentan:

    "Travere Therapeutics Provides Corporate Update and 2022 Outlook
    Published: Jan 10, 2022

    Company positioned for multiple NDA and MAA submissions for accelerated approval in 2022

    SAN DIEGO, Jan. 10, 2022 (GLOBE NEWSWIRE) -- Travere Therapeutics (NASDAQ: TVTX) today announced that, based on preliminary and unaudited financial data, the Company expects net product sales for the fourth quarter of 2021 to be approximately $55 million. For the fiscal year 2021, the Company expects total revenue of $227 million, inclusive of approximately $211 million in net product sales and approximately $16 million in licensing and collaboration revenue. The Company also provided a general update on its development programs, including anticipated milestones for 2022.

    “Following three positive readouts from our pipeline and continued strong execution from our commercial business last year, we enter 2022 with great confidence in our ability to deliver new life-changing therapies to people living with rare disease,” said Eric Dube, Ph.D., chief executive officer of Travere Therapeutics. “We are driven by the potential to make sparsentan a new treatment standard for people living with rare kidney diseases IgA nephropathy and FSGS, if approved. We remain on track for our planned NDA and MAA submissions, the first of which could result in an approval of sparsentan for IgA nephropathy in the U.S. as early as the end of this year. Additionally, with recent clinical proof of concept supporting pegtibatinase, we are in position to engage with regulators and establish the next steps for a pivotal program to further advance this therapy as the first potential treatment targeting the underlying deficiency in classical homocystinuria.”

    Program Updates and Anticipated Upcoming Milestones

    The Company continues to advance its investigational Dual Endothelin Angiotensin Receptor Antagonist (DEARA) sparsentan for the treatment of IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) following previously reported positive topline interim results from the ongoing pivotal Phase 3 PROTECT and DUPLEX studies. The following upcoming milestones are anticipated in 2022:
    In the first quarter of 2022, the Company expects to submit a New Drug Application (NDA) for accelerated approval of sparsentan for IgAN in the U.S.
    In the first half of 2022, the Company plans to provide additional estimated glomerular filtration rate (eGFR) data from the ongoing pivotal Phase 3 DUPLEX Study of sparsentan in FSGS to the U.S. Food and Drug Administration (FDA) to support a potential NDA submission for accelerated approval. Should additional eGFR data from the study be supportive as expected, the Company plans to submit an NDA for accelerated approval of sparsentan for FSGS in the U.S. in mid-2022.
    In collaboration with its partner Vifor Pharma, the Company expects to submit a combined IgAN and FSGS Marketing Authorisation Application (MAA) in mid-2022 for conditional marketing authorization of sparsentan in Europe.
  • m
    martin
    So long as money leaves the Biotech space, LGND shares will be struggling against a stiff current.

    Since LGND has no blockbusters that might lead to near-term (6-18 months) improvements in their prospects for earnings, the share price is unlikely to see a sudden re-rating from such an event.

    Long term is great - but this is not a market willing to price long-term gains in the face of Fed tightening, and balance sheet reduction. The discount rate to be applied to those long-term earnings must b increased, i.e. share prices re-rated lower.
  • M
    Melissa
    More Sugemalimab Results: CStone announces phase 2 GEMSTONE-201 trial met primary endpoint of objective response rate (ORR) in patients with relapsed or refractory extranodal natural killer/T-cell lymphoma. (R/R ENKTL). CStone to file another NDA based on the results.
  • l
    longvrts
    Remdesivir news: GILD CEO O'Day states in Bloomberg interview that FDA working "really collaboratively" with GILD on outpatient Remdesivir infusion. FDA marketing approval expected within 1-2 weeks. In terms of patient counts, 10 million CV19 pts worldwide have received Remi; more than 3 out of 5 hospitalized pts in US receive Remi. LGND receives Captisol related payments of approx 3% of global Remi sales:

    "BusinessPrognosis

    Gilead Says FDA Verdict on Outpatient Remdesivir Likely Soon
    Drug could fill a void as other treatment supplies remain thin
    Drugmaker also looking at future combination Covid therapies

    ByRobert Langreth
    January 10, 2022, 2:07 PM PSTUpdated onJanuary 10, 2022, 2:33 PM PST

    2:25
    Share this article
    @RobertLangreth
    + Get alerts for Robert Langreth

    U.S. regulators may decide within a week or two whether to approve a shorter course of Gilead Sciences Inc.’s Covid-19 drug remdesivir that could be used for patients outside the hospital, Chief Executive Officer Daniel O’Day said in an interview.

    A five-day course of the infused drug is already a mainstay for hospitalized Covid patients. Gilead has applied for U.S. clearance of a three-day course that could be used in the outpatient setting, after a big trial last year showed it could sharply reduce hospitalizations in at-risk patients.

    Officials at the U.S. Food and Drug Administration “are working really collaboratively with us, quickly with us,” O’Day said in the interview. “Everything is moving really fast.”

    The U.S. Food and Drug Administration declined to comment on its timeline for a decision.

    If approved, outpatient remdesivir, or Veklury, could provide another treatment option to manage the omicron surge. While doctors can legally prescribe the outpatient regimen now, as the drug is already on the market for hospitalized patients, many doctors are likely to wait for an official blessing from regulators before employing the treatment widely for outpatients.

    An an infused drug, remdesivir is more complicated to administer than the Pfizer Inc. Covid pill Paxlovid. But Gilead has an abundance of supply on hand, O’Day said in the interview. By contrast, supplies of Pfizer’s drug are limited in the short term as the company ramps up supply.

    Pill Option
    “We are ready to go once we have the approval,” O’Day said in the interview. The drug works against all variants including omicron, and the company has a distribution system ready to ship the drug upon approval for the new use, O’Day said.

    Meanwhile, O’Day said that Gilead is working hard to develop a chemical cousin of remdesivir that could be given as a pill. That oral drug is about to begin human trials. If it works, it could be combined with other drugs to treat Covid, he said.

    Gilead’s long experience with HIV has showed that drug combinations are one way to counter a continually mutating virus. If Covid keeps evolving, combination therapies may be needed in the long run.

    “There is no doubt in my mind” that Covid will continue to mutate, O’Day said. “We want to be prepared for that.”

    Globally, remdesivir has been used by more than 10 million Covid patients to date, O’Day said in a conference presentation earlier on Monday. In the U.S. more than 3 out of 5 hospitalized patients are getting it, he said."
  • l
    longvrts
    1/10 Zimberelimab news: Arcus Bio provides update on Zimberelimab clinical trials. Zimbe is included in 7 trials, including one registrational trial ARC-10. Arcus will have $1.4 Billion in cash after GILD opt-in payment to push forward with trials. Zimbe is an OmniAb derived mAb that is licensed to Gloria Pharma in greater China, Taiho Pharm in Japan and Arcus Bio in US+EU+ROW. Zimbe recently received marketing approval in China. LGND will receive regulatory and commercial milestones, and royalties from global sales:

    "Arcus Biosciences Provides Update on Clinical Programs, Including Key 2022 Milestones
    January 10, 2022

    Six clinical-stage molecules targeting TIGIT, the adenosine axis (CD73 and dual A2a/A2b), HIF-2a and PD-1 continue to advance

    Multiple datasets are expected in 2022, including presentations planned for domvanalimab and etrumadenant in 1L PD-L1 high non-small cell lung cancer (NSCLC; ARC-7), quemliclustat in pancreatic cancer (ARC-8), and pharmacokinetic/pharmacodynamic data for AB521, Arcus’s HIF-2a inhibitor
    Data from ARC-4, a randomized Phase 1/1b study in second- and third-line EGFR-mutation positive (EGFRm+) NSCLC, did not show differentiated clinical activity for the etrumadenant-based combination, and this setting has been de-prioritized
    Arcus and Gilead plan to initiate several new Phase 2 and Phase 3 studies evaluating intra- and cross-portfolio combinations targeting areas of high unmet need in 2022
    Arcus’s cash position will nearly double to $1.4 billion upon receipt of option payments from Gilead in early Q1

    HAYWARD, Calif.--(BUSINESS WIRE)-- Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, today provided updates on clinical programs and key milestones anticipated in 2022.

    “Our priorities for 2022 are clear and unambiguous—to flawlessly execute on the expansion of our global clinical programs which will include more than 10 randomized Phase 2 and 3 studies. We also expect to present randomized datasets from ARC-7 and ARC-8 at medical meetings and generate early data for AB521 that will clarify its potential as a best-in-class molecule,” said Terry Rosen, Ph.D., Chief Executive Officer of Arcus Biosciences. “Our strong cash position and the support from our partner Gilead Sciences enable earlier investment to intelligently advance a broad development plan for our novel and potentially practice-changing combinations to treat cancer.”
  • l
    longvrts
    Rylaze news: Jazz Pharma announces revenue goals by 2025. In the oncology plus cannabidiol grouping they are projecting $2.5 Billion/yr. This implies Rylaze revenue of approx $500 Million- after accounting for Zepzelca and Epidiolex sales- which is a significant boost from previous projections:

    "Vision 2025 includes the following expectations:

    1. Commercial: Generating $5 billion in revenue in 2025

    -Approximately $2.0 billion from oxybate franchise, which includes Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution in narcolepsy and idiopathic hypersomnia, Xyrem® (sodium oxybate) oral solution and royalties from Xyrem authorized generics.

    -Approximately $2.5 billion from Epidiolex/Epidyolex® (cannabidiol) and oncology franchise, including new products Zepzelca (lurbinectedin) and Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn).

    -Approximately $0.5 billion from additional growth opportunities, internal clinical development pipeline and future corporate development."
  • A
    Anonymous
    Hard to attract investors in LGND when it historically trades like this for no fundamental reason
  • l
    longvrts
    Remdesivir news: France to adopt new European Society of Clinical Microbiology and Infectious Diseases guidelines which recommend use of Remdesivir early in the infection cycle. LGND receives Captisol related payments which approximate 3% of Remdesivir global sales:

    "Should remdesivir be recommended in France in the early stage of COVID-19

    Martin Martinot

    Open AccessPublished:January 02,

    2022DOI:https://doi.org/10.1016/j.ijid.2021.12.359
    PlumX Metrics

    Highlights

    Due to the Discovery trial French recommendations do not include remdesivir.

    New COVID-19 variants are responsible of high viral loads and antivirals are lacking.

    Following the ESCMID guidelines, remdesivir should be re-evaluated in France.
    Key words
    SARS-CoV-2
    Remdesivir
    COVID-19
    guidelines
    France
    Coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a raging pandemic. Remdesivir, an RNA-dependent RNA polymerase (RdRP) inhibitor, was the first antiviral drug to be approved for SARS-CoV-2 in the USA (Beigel et al., 2020) and Europe (European Medicine Agency, 2020) and affects the hospital length of stay but not mortality (Goldman et al., 2020). The Solidarity and Discovery trials did not find clinical benefit from the use of remdesivir in COVID-19 treatment (Ader et al., 2021, Consortium et al., 2021). However, most patients included in these trials admitted to hospital for COVID-19, were symptomatic for >7 days and required oxygen support at a time where the inflammatory process is predominant and antiviral drugs are less efficient. The authors of the Discovery study limited their conclusion to symptomatic patients who were hospitalized for >7 days and required oxygen support. Note that numerous guidelines still include remdesivir in their strategy, such as the Infectious Diseases Society of America guideline for hospitalized patients with noncritical COVID-19 (ISDSA,2021) and the new European (European Society of Clinical Microbiology and Infectious Diseases) guidelines with conditional recommendation for patients with mild or severe COVID-19 (Bartoletti et al., 2021). Thus far, French recommendations summarized in the COREB guidelines do not include remdesivir, and the French Haute Autorité de Santé did not recommend the refund of remdesivir for hospitalized patients in September 2020.
    Remdesivir (GS-5734) has potent in vitro activity against a range of RNA viruses, including MERS-CoV, SARS-CoV-1 and SARS-CoV-2, and previous studies highlighted the potential benefit in terms of length of hospitalization and trends in reduction of mortality (Bartoletti et al., 2021, Infectious Diseases Society of America (IDSA), 2021). Remdesivir has renal and hepatic toxicity and must be regularly monitored, but the Discovery trial did not find significant differences in the occurrence of serious adverse events between the remdesivir and placebo groups (Ader et al., 2021) and these events are less frequent during the 5 day course regimen now recommended. More recently a 3 day-course of remdesivir demonstrated efficacy and safety in treating high-risk non-hospitalized patients with COVID-19 (Hill et al, 2021). Interestingly, independent of clinical trials, in vivo activity of remdesivir is described in profound immunosuppressed patients with persistent viremia and chronic viral phase, which is responsible for persistent clinical symptoms. Sepulcri et al. reported a case of persistent viremia in a patient with mantle cell lymphoma who underwent treatment with rituximab, bendamustine and cytarabine with consequent lymphopenia and hypogammaglobulinemia. Viremia was positive in three out of four COVID-19 clinical relapses and cleared after remdesivir treatment (Sepulcri et al., 2021). We reported a similar case in a 76-year-old woman with B-cell immunodeficiency who presented with severe protracted COVID-19 and persistent SARS-CoV-2 viremia and where remdesivir appeared efficient in clearing viremia during drug administration (Martinot et al., 2021). Remdesivir alone was in fact not efficient by itself in the treatment of heavily immunosuppressed patients with relapses after resolution of treatment and in our cases the emergence of a mutation in RdRP, which was responsible for drug resistance. However, in immunocompetent or less immunosuppressed patients, antiviral action provided by drugs, such as remdesivir, could be of high interest, especially in the earlier stage of COVID-19. Highly efficient drugs acting during this viral phase are still lacking, and the emergence of delta virus with higher viral loads than precedent variants (Blanquart et al., 2021) underscores the need for antiviral agents, and we could hypothesize that antiviral drugs, in conjunction to efficient immune system, could lead to a quick clearance
    Redirecting
    doi.org
  • l
    longvrts
    1/7 and 1/9 Sugemalimab news: EQRx enters into MOU's with CVS and Geisinger to accelerate the commercialization of innovative and cost-effective drugs to members/patients of these 2 health systems. Initial focus will be on 2 oncology lead products, sugemalimab and aumolertinib. Sugemalimab is an OmniAb derived mAb and is licensed to CStone Pharma for greater China and EQRx for US+EU+ROW. Sugemalimab has recently received marketing approval for China and has Breakthrough Therapy Designation in US. LGND will receive milestones and royalties from global sales of Suge:

    Jan 7, 2022 at 8:00 AM EST
    EQRx and Geisinger Sign Memorandum of Understanding to Provide Access to Innovative Cancer Medicines at Radically Lower Costs
    PDF Version
    Provides roadmap to commercial agreement between EQRx and Geisinger, a U.S.-based integrated delivery network
    Potential to provide access to affordable treatments in areas of high-cost burden for more than 1 million people within Geisinger health systems
    CAMBRIDGE, Mass., Jan. 07, 2022 (GLOBE NEWSWIRE) -- EQRx, Inc. (Nasdaq: EQRX), a new type of pharmaceutical company committed to developing and delivering important new medicines to patients at radically lower prices, today announced it has signed a non-binding memorandum of understanding (MOU) with Geisinger, a U.S.-based integrated delivery network. The MOU provides a roadmap for Geisinger and EQRx to enter into a commercial agreement that would give Geisinger’s members and patients access to EQRx’s pipeline of innovative medicines, contingent upon approval by the U.S. Food and Drug Administration (FDA). The MOU contemplates an expansion of the existing long-term strategic collaboration between the two organizations with a shared goal of bringing innovative therapies to the people Geisinger serves, in a financially sustainable way.

    The parties anticipate that the commercial agreement would initially focus on EQRx’s two lead oncology programs, aumolertinib and sugemalimab, and could be expanded to other EQRx pipeline programs. Aumolertinib, an epidermal growth factor receptor (EGFR) inhibitor, and sugemalimab, an anti-PD-L1 antibody, have both shown promising Phase 3 data for the treatment of patients with advanced non-small cell lung cancer (NSCLC).

    “We are committed to partnering with different types of health systems worldwide to increase access to medicines, and we are thrilled to collaborate with Geisinger, a leading integrated delivery network,” said Melanie Nallicheri, chief executive officer of EQRx. “The MOU provides a roadmap for access to future EQRx products, beginning with our two lead oncology programs, and paves the way to delivering these lower-cost, innovative medicines to the more than one million people within Geisinger health systems upon FDA approval.”

    “Our partnership with EQRx is well aligned with Geisinger’s commitment to our community to make better health easier by directly addressing the rising costs of healthcare and medications in particular,” said Mike Evans, chief pharmacy officer of Geisinger. “Ballooning medication costs are placing an unsustainable burden on both patients and the U.S. healthcare system. This partnership marks Geisinger’s commitment to disrupt the status quo and help make lower-cost medications for our patients a reality.”

    January 10, 2022
    EQRx Enters Memorandum of Understanding with CVS Health to Create Cost Savings and Improve Patient Access to Innovative Medicines
    The two companies will explore opportunities for a long-term, strategic partnership spanning the CVS Health enterprise
    Includes CVS Caremark, the leading pharmacy benefit manager in the U.S., covering 1 in 3 Americans – nearly 110 million lives
    Initial focus will be on EQRx’s two lead oncology programs with future therapies expected to follow...
  • A
    Anonymous
    After OmiAb spinoff one has to wonder how Ligand would trade any better with what's left based o. how it trades now
  • A
    Anonymous
    Once you spinoff the antibody platform what do u think the rest of LGND is worth?
    Will be interesting to see how management prices the spinoff
  • A
    Anonymous
    Volume is very low
    MM taking this down
    Feb conference call should be good based on confirmed sales and future projections.
  • d
    domenico
    It is option pricing ?? Is that the reason why we dropping ??? Or there is some bad news ???
  • A
    Anonymous
    last after hour trade of 5400 shares dropped the share price by 9.09
    Rediculious. Just hold
  • l
    longvrts
    Report out: Carfilzomib potentiates immune checkpoint treatment by modulating tumor environment. Checkpoint inhibitors have revolutionized cancer treatment, but only work in ~20% of patients. The Holy Grail has been to find a synergistic treatment that would activate the other 80% of cancer patients. This preclinical study demonstrates that Carfilzomib changes the tumor microenvironment and boosts checkpoint inhibitor efficacy in solid tumors. If this finding translates to the clinical setting, then we're looking at a quantum leap in cancer treatment. Current Carfilzomib revenue is projected at ~$1.2 Billion for '21, and would jump several fold if it can boost checkpoint inhibitor efficacy. LGND gets ascending royalties on global sales; on sales greater than $750 Million the rate is 3%:

    EMBO Mol Med. 2021 Dec 13;e14502. doi: 10.15252/emmm.202114502. Online ahead of print.

    Carfilzomib modulates tumor microenvironment to potentiate immune checkpoint therapy for cancer

    Qian Zhou 1, Jinxia Liang 1, Tong Yang 1, Jin Liu 1, Bo Li 1 2, Yingchang Li 1, Zhenzhen Fan 1, Weida Wang 3, Wensheng Chen 1 4, Sujing Yuan 3, Meng Xu 4, Qigui Xu 5, Zhidong Luan 5, Zhongjun Xia 3, Penghui Zhou 3, Yadong Huang 6, Liang Chen 4 6

    PMID: 34898004 DOI: 10.15252/emmm.202114502

    Free article
    Full text linksCite

    Abstract
    Impressive clinical benefit is seen in clinic with PD-1 inhibitors on portion of cancer patients. Yet, there remains an urgent need to develop effective synergizers to expand their clinical application. Tumor-associated macrophage (TAM), a type of M2-polarized macrophage, eliminates or suppresses T-cell-mediated anti-tumor responses. Transforming TAMs into M1 macrophages is an attractive strategy of anti-tumor therapy. Here, we conducted a high-throughput screening and found that Carfilzomib potently drove M2 macrophages to express M1 cytokines, phagocytose tumor cells, and present antigens to T cells. Mechanistically, Carfilzomib elicited unfolded protein response (UPR), activated IRE1α to recruit TRAF2, and activated NF-κB to transcribe genes encoding M1 markers in M2 macrophages. In vivo, Carfilzomib effectively rewired tumor microenvironment through reprogramming TAMs into M1-like macrophages and shrank autochthonous lung cancers in transgenic mouse model. More importantly, Carfilzomib synergized with PD-1 antibody to almost completely regress autochthonous lung cancers. Given the safety profiles of Carfilzomib in clinic, our work suggested a potentially immediate application of combinational treatment with Carfilzomib and PD-1 inhibitors for patients with solid tumors.

    Keywords: M1 macrophage; M2 macrophage; immunotherapy; tumor microenvironment; tumor-associated macrophage.
  • T
    Thom
    Termination of CVR is official. I wonder if that whisper somehow got construed as bad news.
  • S
    StellaBlue
    Ugh. Why is LGND #$%$ the bed this badly? Earnings for the quarter down, but for the year look increased over last, forward PE only around 20, compared to all the over-inflated prices in this market. I'm no pro - what am I missing?
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