Celldex Therapeutics, Inc. (CLDX)
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"Acquisition Includes TAVNEOS® (avacopan), a First-in-Class Medicine for Patients With Serious Autoimmune Disease
Tavneos Adds to Amgen's Decades-Long Leadership in Inflammation and Nephrology
THOUSAND OAKS, Calif. and SAN CARLOS, Calif., Aug. 4, 2022 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and ChemoCentryx, Inc., (NASDAQ: CCXI), a biopharmaceutical company focused on orally administered therapeutics to treat autoimmune diseases, inflammatory disorders and cancer, today announced that the companies have entered into a definitive agreement under which Amgen will acquire ChemoCentryx for $52 per share in cash, representing an enterprise value of approximately $3.7 billion.
ChemoCentryx Logo
ChemoCentryx Logo
"The acquisition of ChemoCentryx represents a compelling opportunity for Amgen to add to our decades-long leadership in inflammation and nephrology with TAVNEOS, a transformative, first-in-class treatment for ANCA-associated vasculitis," said Robert A. Bradway, chairman and chief executive officer at Amgen. "We are excited to join in the TAVNEOS launch and help many more patients with this serious and sometimes life-threatening disease for which there remains significant unmet medical need. We also look forward to welcoming the highly skilled team from ChemoCentryx that shares our passion for serving patients suffering from serious diseases."
"A fierce commitment to improving human lives is the bond that unites Amgen and ChemoCentryx today," said Thomas J. Schall, Ph.D., president and chief executive officer of ChemoCentryx. "Last year, after 25 years of proud history, we at CCXI delivered on our founding promise with the approval of TAVNEOS for patients with anti-neutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-associated vasculitis). It is an honor to now join Amgen's great mission, and together begin a bright new era bringing landscape-shaping medicines like TAVNEOS to those who will benefit most."
TAVNEOS is an orally administered selective complement component 5a receptor inhibitor. It was approved by the U.S. Food and Drug Administration in October 2021 as an adjunctive treatment for adult patients with severe active ANCA-associated vasculitis, specifically granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) (the two main forms of ANCA-associated vasculitis), in combination with standard therapy.
ANCA-associated vasculitis is an umbrella term for a group of multi-system autoimmune diseases with small vessel inflammation. Inflamed vessels may rupture or become occluded giving rise to a broad array of clinical symptoms and signs related to a systemic inflammatory response which may result in profound injury and dysfunction in the kidneys, lungs and other organs.
Amgen is a leader in inflammation and nephrology. The company's inflammation portfolio includes Otezla®, ENBREL®, TEZSPIRE®, AMGEVITA™ (a biosimilar to HUMIRA®), RIABNI™ (a biosimilar to Rituxan®), and AVSOLA® (a biosimilar to REMICADE®). Amgen's pipeline includes four innovative Phase 2 inflammation medicines – efavaleukin alpha for systemic lupus erythematosus and ulcerative colitis, ordesekimab for celiac disease, rocatinlimab for atopic dermatitis and rozibafusap alfa for systemic lupus erythematosus – as well as ABP 654, a biosimilar to STELARA® that is in Phase 3 development. Amgen's nephrology portfolio includes EPOGEN®, Aranesp®, Parsabiv® and Sensipar®.
U.S. sales of TAVNEOS in the first quarter of 2022, the first full quarter of sales, were $5.4 million. TAVNEOS is also approved in major markets outside the U.S., including the European Union and Japan. Vifor Fresenius Medical Care Renal Pharma Ltd. will retain exclusive rights to commercialize TAVNEOS outside the U.S., except in Japan where Kissei Pharmaceutical Co., Ltd. holds commercialization rights and Canada where Otsuka Canada Pharmaceutical holds commercialization rights.
In addition to TAVNEOS, ChemoCentryx has three early-stage drug candidates that target chemoattractant receptors in other inflammatory diseases and an oral checkpoint inhibitor for cancer.
The transaction has been unanimously approved by each company's board of directors. The transaction is subject to ChemoCentryx stockholder approval, regulatory approvals and other customary closing conditions, and is expected to close in the fourth quarter of 2022.
Amgen management will comment further on the ChemoCentryx transaction on its Q2 earnings call today.
PJT Partners acted as financial advisor to Amgen and Wachtell, Lipton, Rosen & Katz is serving as its legal advisor. Goldman Sachs & Co. LLC acted "
"Matrix Biol. 2022 Jul 28;S0945-053X(22)00094-4. doi: 10.1016/j.matbio.2022.07.005. Online ahead of print.
Mast Cell Chymase Has a Negative Impact on Human Osteoblasts
Thomas Lind 1, Fabio Rabelo Melo 2, Ann-Marie Gustafson 3, Anders Sundqvist 4, Xinran O Zhao 2, Aristidis Moustakas 2, Håkan Melhus 5, Gunnar Pejler 2
PMID: 35908613 DOI: 10.1016/j.matbio.2022.07.005
Cite
Abstract
Mast cells have been linked to osteoporosis and bone fractures, and in a previous study we found that mice lacking a major mast cell protease, chymase, develop increased diaphyseal bone mass. These findings introduce the possibility that mast cell chymase can regulate bone formation, but the underlying mechanism(s) has not previously been investigated. Here we hypothesized that chymase might exert such effects through a direct negative impact on osteoblasts, i.e., the main bone-building cells. Indeed, we show that chymase has a distinct impact on human primary osteoblasts. Firstly, chymase was shown to have pronounced effects on the morphological features of osteoblasts, including extensive cell contraction and actin reorganization. Chymase also caused a profound reduction in the output of collagen from the osteoblasts, and was shown to degrade osteoblast-secreted fibronectin and to activate pro-matrix metallopeptidase-2 released by the osteoblasts. Further, chymase was shown to have a preferential impact on the gene expression, protein output and phosphorylation status of TGFβ-associated signaling molecules. A transcriptomic analysis was conducted and revealed a significant effect of chymase on several genes of importance for bone metabolism, including a reduction in the expression of osteoprotegerin, which was confirmed at the protein level. Finally, we show that chymase interacts with human osteoblasts and is taken up by the cells. Altogether, the present findings provide a functional link between mast cell chymase and osteoblast function, and can form the basis for a further evaluation of chymase as a potential target for intervention in metabolic bone diseases."
"Eur J Immunol. 2022 Jul 20. doi: 10.1002/eji.202149698. Online ahead of print.
Agonistic anti-CD27 antibody ameliorates EAE by suppressing IL-17 production
Isabel Vogel 1 2 2, Valerie Acolty 1, Tibor Keler 3, Stanislas Goriely 1, Oberdan Leo 1, Muriel Moser 1
Affiliations
1Laboratory of Immunobiology, Université Libre de Bruxelles (ULB) - IBMM, Rue des Prof. Jeener et Brachet 12, Gosselies, 6041, Belgium.
2NeuVasQ Biotechnologies, Rue Auguste Piccard 48, Gosselies, 6041, Belgium.
3Celldex Therapeutics, Inc., 53 Frontage Road, Suite 220, Hampton, NJ, 08827, USA.
PMID: 35856659 DOI: 10.1002/eji.202149698
Abstract
CD27/CD70 costimulation enhances T-cell survival, memory formation and Th1-cell differentiation and effector function. In addition to promoting Th1 responses, CD27 signalling has been shown to exert a negative regulatory role on IL-17 production, resulting in increased sensitivity of CD27 KO mice to experimental autoimmune encephalomyelitis (EAE). By inducing EAE in full CD27 KO mice, and in a novel, T-cell specific CD27 KO mouse strain (CD4-Cre x CD27flox/flox ), we demonstrate herein that CD27 engagement by its natural ligand (CD70) suppresses IL-17 production in a cell autonomous fashion. We further show that CD27 engagement by an agonistic antibody given after EAE induction or at symptom onset similarly suppresses IL-17 production by activated CD4+ T cells infiltrating the inflamed central nervous system (CNS) while IFNγ production was unaffected, leading to an amelioration of inflammatory-related symptoms. These findings propose CD27 costimulation as a potential candidate for therapeutic manipulation to treat autoimmune and autoinflammatory diseases characterized by excessive IL-17 production. This article is protected by copyright. All rights reserved."
Celldex: Barzolvolimab Plus Bispecific Antibodies Advancement
Jul. 14, 2022 3:32 PM ETCelldex Therapeutics, Inc. (CLDX)IBB, XBI, ARKG,
Terry Chrisomalis
Marketplace
Summary
Proof of concept has been established in using Barzolvolimab in treating Chronic spontaneous urticaria and Chronic inducible urticaria patients in phase 1b studies.
One phase 2 study with Barzolvolimab treating Chronic spontaneous urticaria patients has been initiated with second phase 2 study in Chronic inducible urticaria expected to start 2nd half of 2022.
Potential to expand the use of Barzolvolimab in other inflammatory disorders such as Prurigo Nodularis and Eosinophilic esophagitis.
CDX-1140 and CDX-527 are oncology drugs being advanced in the pipeline; CDX-1140 with CD40 targeting head/neck cancer and lung cancer, CDX-527 bispecific antibody targeting ovarian cancer.
https://seekingalpha.com/article/4523394-celldex-barzolvolimab-plus-bispecific-antibodies-advancement?mailingid=28386450&messageid=investing_ideas&serial=28386450.66011&source=email_investing_ideas&utm_campaign=Stock+Ideas+Recurring++2022-07-15&utm_content=investing_ideas_control&utm_medium=email&utm_source=seeking_alpha&utm_term=Investing+Ideas
Form 8-K Celldex Therapeutics, For: Jul 15
BY 10K Wizard
— 4:02 PM ET 07/18/2022
http://archive.fast-edgar.com/20220718/A3B4822C8Z2289Z222ZS2ZZZ5PQTZ2Y2324G
Filed on: July 18, 2022
"Billionaire Andreas Halvorsen Bets Big on These 2 High-Upside Stocks
CLDX
+2.20%
Fri, July 8, 2022 at 6:26 AM
In this article:
CLDX
+2.20%
Even after some recent positive trading sessions, the stock markets are still registering heavy losses this year. The S&P is down 18%, and the NASDAQ remains in bear territory with a 26% year-to-date loss.
But these broad-based market losses have also opened up opportunities, as many stocks have fallen for no fault of their own. Some of the Street’s most legendary investors are not shying away from buying in, even in this bearish environment. Andreas Halvorsen, a former Tiger Cub and the billionaire head of the Viking Global Investors hedge fund, is one of them, and has been going all-in on several stocks with high upside potential.
Halvorsen, who’s trading acumen has built Viking into a $47 billion giant, has followed something of a blanket strategy in building his fund. Viking covers some 1,000 publicly trading firms, and uses ‘thoughtful risk-taking’ to generate compelling returns for investors. And in recent weeks, Halvorsen has bought heavily into two high-risk, high-reward stocks.
According to TipRanks' database, these are stocks with Buy ratings, and offering investors triple-digit upside potentials. We can take a closer look at them, and at the analyst commentary, to find out what else may have brought them to Halvorsen’s attention.
Celldex Therapeutics (CLDX)
The first Halvorsen pick we’ll look at is Celldex, a biopharmaceutical firm working on new treatments for devastating disease conditions that lack adequate existing treatment. Specifically, Celldex is using monoclonal and bispecific antibodies to create targeted therapies that will engage the patients’ immune systems for great effect against cancers and inflammatory diseases.
Celldex has three general research tracks – oncology, inflammatory, and bispecific – featuring five drug candidates. Three of the candidates are in clinical trials, and two in preclinical research stages. The inflammatory track is subject of most of the current research, with the leading drug candidate, barzolvolimab (CDX-0159) being tested in no fewer than 4 clinical trials. These trials are testing the drug against several conditions, including chronic inducible urticaria, chronic spontaneous urticaria (CSU), prurigo nodularis, and eosinophilic esophagitis.
The second of those conditions, CSU, is relatively one of the company’s most advanced trials. In two recent announcements, Celldex released interim data on the Phase 1b trial, which indicated a ‘rapid, profound and durable responses across multiple dosing groups with favorable safety profile.’ These results led to the announced initiation of a Phase 2 study, with the first patients dosed last month.
Turning to Halvorsen’s holdings in CLDX, we find that his Viking Global Investors fund owned 1,846,647 shares at the end of 1Q22. According to regulatory filings, Halvorsen has since picked up another 519,738 shares, and as of May 31 this year, the fund owns a total of 2,366,385 shares in Celldex. At current stock prices, this stake is worth more than $66.38 million. Halvorsen’s holding gives his hedge a 5.1% ownership in the biotech company.
RCelldex has also caught the attention of SVB analyst Thomas Smith, who points out the clinical trial successes of barzolvolimab as the key to this company: "These [CSU] data reinforce our view that barzolvolimab, with its unique mast cell-depleting mechanism of action, is tracking toward a differentiated profile that could unlock a significant commercial opportunity in treating chronic urticarias and mast cell-driven diseases broadly.”
"We continue to see a blockbuster opportunity for barzolvolimab in chronic urticarias and other mast cell-driven diseases based on a potentially differentiated profile that has featured unprecedented efficacy in CIndU patients utilizing a single 3.0mg/kg dose,” the analyst added.
It should be unsurprising, then, that Smith rates CLDX an Outperform (i.e. Buy). Not to mention his $68 price target puts the upside potential at 162%. (To watch Smith’s track record, click here)
There is some evidence here that Wall Street generally is in agreement with the bullish view on Celldex. The stock has picked up 4 recent analyst reviews – and they are unanimous that this is a stock to buy, giving CLDX its Strong Buy consensus rating. The shares are priced at $25.94, and their average target of $66.50 implies a robust upside of 156% from current levels."
"Eur Respir J. 2022 Jul 1;2101431. doi: 10.1183/13993003.01431-2021. Online ahead of print.
Adverse roles of mast cell chymase-1 in chronic obstructive pulmonary disease
Gang Liu 1, Andrew G Jarnicki 2, Keshav R Paudel 1, Wenying Lu 3, Ridhima Wadhwa 1, Ashleigh M Philp 1 4, Hannelore Van Eeckhoutte 5, Jacqueline E Marshall 1, Vamshikrishna Malyla 1, Angelica Katsifis 1, Michael Fricker 6, Nicole G Hansbro 1, Kamal Dua 1 7, Nazanin Z Kermani 8, Mathew S Eapen 3, Angelica Tiotiu 9 10, K Fan Chung 9, Gaetano Caramori 11, Ken Bracke 5, Ian M Adcock 9, Sukhwinder S Sohal 3, Peter A Wark 6, Brian G Oliver 12, Philip M Hansbro 13 6
Affiliations
1Faculty of Science, Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Sydney, New South Wales, Australia.
2Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria, Australia.
3Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Launceston, Tasmania, Australia.
4St Vincent's Medical School, University of New South Wale Medicine, University of New South Wale, Sydney, New South Wales, Australia.
5Laboratory for Translational Research in Obstructive Pulmonary Diseases, Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.
6Priroity Research Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, New South Wales, Australia.
7Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW, Australia.
8Department of Computing, Data Science Institute, Imperial College London, United Kingdom.
9National Heart & Lung Institute, Imperial College London, United Kingdom.
10Department of Pulmonology, University Hospital of Nancy, France.
11UOC di Pneumologia, Dipartimento di Scienze Biomediche, Odontoiatriche e delle Immagini Morfologiche e Funzionali (BIOMORF), Università di Messina, Italy.
12Faculty of Science Life science, Woolcock Institute and School of Life Science, University of Technology Sydney, Sydney, New South Wales, Australia.
13Faculty of Science, Centre for Inflammation, Centenary Institute and University of Technology Sydney, School of Life Sciences, Sydney, New South Wales, Australia philip.hansbro@uts.edu.au.
PMID: 35777766 DOI: 10.1183/13993003.01431-2021
Full text linksCite
Abstract
Background: COPD is the third leading cause of death worldwide. Cigarette smoke (CS)-induced chronic inflammation inducing airway remodelling, emphysema and impaired lung function is the primary cause. Effective therapies are urgently needed. Human chymase-1 (hCMA1) and it's ortholog mCMA1/mouse mast cell (MC) protease-5 (mMCP5) are exocytosed from activated MCs and have adverse roles in numerous disorders, but their role in COPD is unknown.
Methods: We evaluated hCMA1 levels in lung tissues of COPD patients. We used mmcp5-deficient (-/-) mice to evaluate this proteases' role and potential for therapeutic targeting in CS-induced experimental COPD. We also used ex vivo/in vitro studies to define mechanisms.
Results: The levels of hCMA1 mRNA and CMA1+ MCs were increased in lung tissues from severe compared to early/mild COPD patients, non-COPD smokers and healthy controls. Degranulated MC numbers and mMCP5 protein were increased in lung tissues of wild-type (WT) mice with experimental COPD. mmcp5 -/- mice were protected against CS-induced inflammation and macrophage accumulation, airway remodelling, emphysema and impaired lung function in experimental COPD. CS extract challenge of co-cultures of MCs from WT but not mmcp5 -/- mice with WT lung macrophages increased in TNF-α release. It also caused the release of CMA1 from human MCs, and recombinant hCMA-1 induced TNF-α release from human macrophages. Treatment with CMA1 inhibitor potently suppressed these hallmark features of experimental COPD.
Conclusion: CMA1/mMCP5 promotes the pathogenesis of COPD, in part, by inducing TNF-α expression and release from lung macrophages. Inhibiting hCMA1 may be a novel treatment for COPD."
1. Complete Response = 57% at low dose 1.5 mg/kg; this is 2-fold better efficacy than Xolair and ligelizumab at their respective low doses.
2. Barzo mature high dose results still to be announced: 4.5 mg/kg will be especially interesting.
3. More than 40% of patients in this trial were Xolair refractory (which means they were also ligelizumab refractory because of similar mechanism of action). Essentially these CSU patients have run out of treatment options, yet close to 60% were cured with Barzo treatment!
This is what it's all about!
"Front Allergy. 2022 May 25;3:867227. doi: 10.3389/falgy.2022.867227. eCollection 2022.
Disease Impact, Diagnostic Delay, and Unmet Medical Needs of Patients With Cholinergic Urticaria in German-Speaking Countries
Sabine Altrichter 1 2, Emilia Mellerowicz 1, Dorothea Terhorst-Molawi 1 3 4, Eva Grekowitz 1 3, Karsten Weller 1 3, Marcus Maurer 1 3
Affiliations
1Institute for Allergology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universitätzu Berlin, Berlin, Germany.
2Department of Dermatology and Venerology, Kepler University Hospital, Linz, Austria.
3Fraunhofer Institute for Translational Medicine und Pharmacology ITMP, Allergology and Immunology, Berlin, Germany.
4Clinical Physiology/Nutritional Medicine, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
PMID: 35769577 PMCID: PMC9234879 DOI: 10.3389/falgy.2022.867227
Abstract
Background: Cholinergic urticaria (CholU) is a common type of chronic inducible urticaria. Little is known about the burden of the disease and its unmet medical needs.
Aim: To characterize the unmet medical needs of patients with CholU.
Methods: Patients with CholU (n = 111) took part in a German online survey that assessed their symptoms, diagnostic delay, impact on daily life, quality of life (QoL), and their experience with physician care.
Results: Virtually all patients reported typical signs and symptoms of CholU, i.e., whealing (93.7%) and itching (91.9%), in response to typical trigger situations, such as physical activity, passive warming, or stress. Despite this, patients reported a marked diagnostic delay of 30.2 months (range from 0 to 279 months). Only 38% of the patients received a blood examination, and only 16% underwent provocation testing for diagnosing CholU, as recommended by the international guidelines. Physician contacts were common, but patient satisfaction with their disease management was low. In total, 90.1% of the patients stated to have an uncontrolled disease, resulting in a strong impact on their everyday activities, sleep, and QoL.
Conclusion: Patients with CholU exhibit many important unmet needs, and improvement in the diagnostic workup and patient care is needed, as are better treatment options."