Oncology Highlights - January 2019
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Enjoy reading! - The SMS-oncology team
Macrophages can either support cancer cell growth or hinder it by phagocytosis. CD47 signal expressed by most tumors can silence the macrophages into a deep sleep and prevent them from eating. In a recent study published in Nature Immunology, researchers found that altering macrophage energy metabolism can overcome this signal and act like a waking alarm to rouse macrophages to attack the tumor. The team primed the macrophages with CpG oligonucleotide, a Toll-like receptor 9 agonist, which effects the carbon metabolism of macrophages andsubsequently unleashes the antitumor activity. Stimulated macrophages begin to utilize both glutamine and glucose as a fuel for their energy.Their findings indentify carbon metabolism to be a potential target and a crucial component of antitumor response by these defence cells. Even though the researchers show that this approach as monotherapy was enough to reduce tumors and prolong survival in mice, a dual theraphy with. (Image source: Acrobiosystems)
The team at the Institute of Cancer Research (ICR) developed an Artificial Intelligence (AI) tool that looks for misshapen nuclei of the cells within tumors to pick out women with aggressive ovarian cancer. Their AI based automated histology image and spatial statistical analyses defines cancer morphological diversification within the tumor microenvironment. Scanning 514 advanced ovarian cancer biopsies, the team identified a correlation between DNA repair defects and nuclei shapes. Nuclei with high shape variation had lower activity of BRCA1 and other hidden key DNA repair genes, which can be missed when testing only for BRCA genes. Tumors with DNA repair mutations are susceptible to and can be targeted with PARP inhibitors. Besides this, in the study published in Nature Communications, Galectin-3 was identified as a potential novel immune evasion route. High level of expression of galectin-3 was detected within misshaped nuclei cluster, which is a negative modulator of immune cells and can be a potential target for immunotherapies. (Image source: Heindl et al., Nature Communications 2019.)
Biotech and Pharma did not stall during January in oncology:
- Lilly buys Loxo: The Indianapolis based drug giant announced to purchase a small start-up, Loxo Oncology, for $8B. Lilly will gain access to Loxo’s pipeline targeting cancers that are dependent on single gene mutations including LOXO-292 (RETi), LOXO-305 (BETi) and TRKi. Broadening its cancer portfolio, Lilly’s CEO said their cancer treatment pipeline will leave CAR-T therapies for cancer and gene therapy for rare diseases to others for now.
- BMS inks $74B to buy Celgene: Heating up the competition in block-buster cancer drugs, BMS is acquiring Celgene with an expectation of $15B a year return from its late-stage pipeline. The combined company will have 9 products including cancer immunotherapies, hematology and inflammation. The acquisition marks the combination two of the world’s top 10 global drug makers. As a reaction to the acquisition, BMS’ shares dropped with 15% while Celgene’s stock rocketed up to 31%. After the news, Celgene continues wrapping up deals with small IO start-ups including Boston based Kyn Therapeutics and Obsidian Therapeutics.
- Ribon therapeutics raises $65M: Developer of PARP inhibitors raised a $65M Series B led by Novartis Venture Fund. The company is creating an integrated platform to interrogate monoPARPs and discover and develop small molecule inhibitors. In oncology, Ribon’s lead programs are the PARP7 inhibitors initially targeting squamous cell carcinoma of lung.
- Exscientia and Roche sign a deal: The British AI-driven drug discovery company Exscientia raised a €23M Series B round and announced a partnership with Roche worth up to €60M. AI platform is developed to reduce the time and costs of drug-discovery at least 4-5 fold. Already partnered with Celgene, GSK and Evotec, Exscientia will apply its Centaur Chemist platform to design pre-clinical drug candidates for Roche.
- Sanofi packs with Regeneron and BioNTech: Sanofi is powering up its existing collaborations: first, with Regeneron, Sanofi restructured their IO programs for the collaborative development of AxCD3 and MUC16xCD3 bispecifics. The French drug maker will pay $462M for rights to opt-in to development and marketing of these candidates. Second big deal is Sanofi’s €80M equity investment in the German biotech BioNTech. The two have agreed to co-develop a cancer vaccine based on intratumoral injection of cytokine mRNA into solid tumors.
The Committee for Medicinal Products for Human Use (CHMP) recommended granting marketing authorization for:
- Vizimpro (dacomitinib, Pfizer) for the first-line treatment of locally advanced or metastatic NSCLC with EGFR activating mutations as monotherapy. The irreversible EGFR kinase inhibitor was approved in the United States and Japan in 2018 and would represent an advance in the treatment of metastatic NSCLC, since it is estimated that in 2018 more than 2M new cases were diagnosed in the world.
The CHMP extended the therapeutic indication for:
- Keytruda (pembrolizumab, Merck) in combination with carboplatin and either paclitaxel or nab-paclitaxel for the first line treatment of metastatic squamous NSCLC in adults patients. The affirmative CHMP feedback was based on data from the phase III KEYNOTE-407 study in which PD1i plus chemotherapy improved overall survival (OS), response rates, and duration of response.
- Tecentriq (atezelizumab, Roche) in combination with bevacizumab, paclitaxel and carboplatin for the first-line treatment of adult patients with metastatic NSCLC. The PD-L1 inhibitor is recommended only after failure of appropriate targeted therapies for the patients with EGFR mutant or ALK-positive NSCLC. Exploratory analysis of the IMpower150 study showed improved OS and progression-free survival (PFS) in these patients.
The FDA granted approval for:
- Caboteyx (cabozantinib, Exelixis) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (a kinase inhibitor). The small molecule inhibits c-Met, VEGFR2 as well as AXL and RET. The drug has previously been approved for thyroid and renal cell carcinoma. FDA approval follows the European approval in this indication last November. Exelixis’ partner Ipsen will market the drug.