Parkinson´s; 3-D tumors; Personalized normal control genome; EUR 442 mil for Ganymed Pharmaceuticals; Pfizer´s stop of PCSK9 mAb

What has caught my attention in Pharma, Biotech, Biomedicine and Science in the last two weeks? Here is a selection of the news, articles, papers, findings, risings, falls as I have read, heard, discussed, been involved in. Very subjective, not pretending to be comprehensive or representative. Just my selection.

MY MedScan in cw 43-44. There have been a lot happening around these days, shortened in my country by a holiday on November 1st. Time to slow down a bit and refresh memories on our loved ones who are not anymore with us…And a full coloured autumn with all the neighbor leaves on my lawn which are good for movement on fresh air:-)

Here we go:

26.10.2016: Parkinson´s disease in Nature Outlook

A debilitating disease affecting around 10 million people in the world was described 200 years ago by James Parkinson. Where we are in understanding of underlying mechanisms of the disease, what treatments are available and what treatments could be available in near future? In the Nature Outlook released in October 2016 you can read more from recent and breakthrough findings as published in Nature journals.

27.10.2016: „3-D tumors grown in the lab provide new perspective for cancer drug discovery“

It really could matter whether you grow your cancer cells on a flat surface of a plate or you use a kind of in vivo tumor growth simulation. Exposing such cell communities to potential drugs can give different results as you can see in this release.
Last week I also met a guy from a start-up company in Czech Republic and they offer a system for cell cultivation on a nanofibrous 3-D culture system. They have been able to see assembling of osteosarcoma cells to spheroid-like structures mimicking avascular tumour environment. Probably, worthy to test.

27.10.2016: When sequencing a tumor genome, to what you should compare the results?

Comparison of genetic mutations found in tumours is usually done to a human reference genome. But, as scientists found and published, „a preferred method might be de novo assembly of personalized normal control genome and cancer cell genome, instead of mapping and aligning NGS [next generation sequencing] data to mouse or human reference genome“. Main reason for that is presence of differences (e.g mutations, translocations, etc.) in a DNA of a single organism in comparison to another organism found already in normal cells. When you then compare tumor tissue from such organism to a reference DNA from a database, you can account wrongly these differences as a pathological change of DNA in a tumor.
In addition to the above article and not connected just to cancer, recent analysis showed that we should „rethink the links between genes and disease“ and see whether a gene variant firstly suspected to be involved in a disease is not too common to do so, in other words, it can be harmless. Time to a „radical revision in human genetics“?

31.10.2016 A small German biotech Ganymed Pharmaceuticals was acquired by Astellas for EUR 422 mil

Ganymed Pharmaceuticals is developing antibodies against unique cancer target(s). After July announcement of positive results on significant improvement of gastric patients survival by the mAb targeting Claudin18.2, on October 31 they announced becoming a wholly owned subsidiary of Astellas. For the shareholders, this transaction brings an exit worth EUR 422 millions and future EUR 866 mil in contingent payments if the candidate mAb IMAB362 succeds in clinical development. I would say, very good and congratulations!

Another biotech company with the same investors (Strüngmann Family Office and MIG funds), BioNTech, is also doing well. In September 2016, they announced entering into the strategic collaboration with Genentech ( a member of the Roche group), on developing, manufacturing and commercializing novel messenger RNA (mRNA)-based, individualized cancer vaccines. Worth $ 310 mil plus milestone payments.

1.11.2016 Pfizer stops development of their late stage PCSK9 mAb but what about their small molecule and a vaccine targeting the same molecule?

Bococizumab, a cholesterol-lowering monoclonal antibody, will not be further developed at Pfizer and the company is discontinuing also two outcome clinical studies. The outcome studies should have assessed whether the PCSK9 inhibitor can, besides lowering of LDLc, lower also incidence of cardiovascular diseases. Observing recent performance of Praluent and Repatha sales (both PCSK9 mAbs, approved and launched last year) which are far lower than expected by the launching companies and all the analysts, the Pfizer´s decision is not so surprising. In addition, Pfizer openly said that its Bococizumab faces attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time, induce unwanted antibodies against it and has also higher injection-side reactions.

However, Pfizer has not developed just a PCSK9 mAb. They have a so called „PCSK9 franchise“ which contains besides the advanced mAb also a small molecule and a vaccine targeting PCSK9, both in preclinical stages. What will be the fate of these candidates? Will they be also stopped? By my meaning not, however a need for long-lasting outcome studies can prevent continuation at Pfizer especially when the competitor´s outcome studies with PCSK9 mAbs do not show convincing results.