Avid Bioservices Inc (CDMO)

[biopharm]

Merck paying big bucks for HIF-1a 2a etc downstream Targeting that results in increased MDSCs ...when upstream ...we have flipped PS which would occur first with an anti-PS drug, then takes care of all downstreamers
_________

Targeting HIF-2α as therapy for advanced cancers.

Abstract
Hypoxia-inducible factors (HIF-1α, -2α -3α, and -β) are key factors that control hypoxia-induced carcinogenic pathways. HIF-1α is predominantly involved in the early stages of cancer, whereas HIF-2α is actively involved in the later stages; in addition, chronic (prolonged) rather than acute (short) hypoxia is a feature of metastasis and chemoresistance that occur during the later stages of cancer.

https://www.ncbi.nlm.nih.gov/m/pubmed/29753878/

______


May 21 2019

Merck has struck a deal to buy Peloton Therapeutics for $1.1 billion upfront days before the biotech was due to list on Nasdaq. The deal will give Merck control of an experimental oral HIF-2α inhibitor that could challenge Keytruda for the metastatic renal cell carcinoma (mRCC) market.

Peloton was due to go public this week and raise $150 million or more to bankroll a late-phase trial of HIF-2α inhibitor PT2977 in mRCC patients previously treated with at least one checkpoint inhibitor, such as Merckâ??s Keytruda. But a late offer from Merck has persuaded the biotech to switch lanes, taking a buyout that represents a premium on the IPO terms even before milestones are factored in.

All told, Merck could pay $1.2 billion in milestones on top of the $1.1 billion cash upfront. In return, Merck will gain a drug that is due to move into phase 3 later this year on the strength of data from 55 mRCC patients who had received at least one prior line of therapy.

https://www.fiercebiotech.com/biotech/merck-boosts-late-phase-cancer-pipeline-1-1b-peloton-buy

_________

Tumor cells adapt to the hypoxic microenvironment through the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are heterodimeric proteins composed of an oxygen-sensitive alpha subunit (HIF-1α, HIF-2α, HIF-3α) and a beta subunit (HIF-β/ARNT). Both HIF-1α and HIF-2α are regulated by oxygen-dependent von Hippel-Lindau (VHL)-mediated degradation [6]. HIF-1α and HIF-2α share overlapping target genes and each one also regulates a set of unique targets. These hypoxia-dependent HIF-1α- and HIF-2α-induced genes play important roles in regulating different aspects of tumor biology such as angiogenesis, cell survival, chemo- and radio-resistance, proliferation, tumor cell plasticity, invasion and metastasis, pH regulation and metabolism, resistance to the immune system, and maintenance of cancer stem cells [6,8].

https://www.sciencedirect.com/science/article/pii/S0304383519303167