Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘Cancer Molecular Targets’

Boston – at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference today, preclinical data was presented on a first-in-class antibody-drug conjugate (ADC) targeting guanylyl cyclase c (GCC) expression in pancreatic cancer.

Petter Veiby Ph.D presenting at Molecular Targets press briefing Petter Veiby, Ph.D, Global Head of BioTherapeutics, Oncology DDU at Takeda Pharmaceuticals International Co. in Boston, MA took the assembled press corps through data that showed MLN0264 demonstrated antitumor activity in GCC-pancreatic cancer xenograft models.

In drug development, as in life, timing is everything. The recent FDA approval of Celgene’s nab-paclitaxel (Abraxane) has changed the standard of care in pancreatic cancer.

The 2013 Molecular Targets and Cancer Therapeutics Conference (twitter #targets13) takes place in Boston from October 19-23 at the Hynes Convention Center. It’s a “must attend” meeting for anyone with an interest in cancer drug development and I’m really looking forward it. Boston is an exciting place for cancer research!

Molecular Targets Meeting AppJointly organized by the American Association for Cancer Research (AACR), European Organization for Research and Treatment of Cancer (EORTC) and National Cancer Institute (NCI), it alternates each year between Europe the United States.

The molecular targets meeting program and abstracts are now available online. There’s also a meeting App that’s well worth downloading if you plan to be there.

As for what’s interesting at the meeting – the three media briefings give a flavor of what to expect:

Sunday, Oct. 20, 10 a.m. “Emerging Therapeutics,” including research on investigational drugs AZD9291 and PF-06463922, which have the potential to overcome drug resistance in some lung cancers.

Monday, Oct. 21, 9 a.m. “Overcoming Resistance and Hard-to-Treat Cancers,” including research on a new antibody-drug conjugate MLN0264 for pancreatic cancer and a new nanopharmaceutical CRLX101 for cancers resistant to antiangiogenic drugs.

Tuesday, October 22, 9 a.m. “Guiding Treatment for BRAF- and BRCA-related Cancers,” including updated data on the clinical benefit of the PARP inhibitor BMN 673 and a new diagnostic platform to rapidly identify BRAF mutations.

The AACR press team led by Jeremy Moore have done a good job of identifying some of the exciting new drugs in development.

Readers of blog premium content have already read about the potential of AZD9291 in T790M resistant lung cancer from ECCO 2013 in Amsterdam.  While it looks like the ECCO late-breaker did steal some of the thunder from the molecular targets meeting, there’s going to be more granularity on the compound at AACR, and hopefully some updated clinical data.

There are three AZD9291 posters at the meeting, and I’ll be covering all of these while in Boston:

Sunday, Oct 20, 2013, 12:30 PM – 3:00 PM  A109: AZD9291: an irreversible, potent and selective third generation tyrosine kinase inhibitor (TKI) targeting EGFR activating (EGFRm+) and resistance (T790M) mutations in advanced lung adenocarcinoma.

Monday, Oct 21, 2013, 12:30 PM – 3:00 PM  B212: Integrating the pre-clinical pharmacokinetic, pharmacodynamics, and efficacy data for AZD9291, an oral, irreversible inhibitor of EGFR activating (EGFRm+) and resistant (EGFRm+/T790M) mutations and an active metabolite to predict the human pharmacokinetics and potential efficacious dose in patients.

Monday, Oct 21, 2013, 12:30 PM – 3:00 PM B94 Discovery of and first disclosure of the clinical candidate AZD9291, a potent and selective third-generation EGFR inhibitor of both activating and T790M resistant mutations that spares the wild type form of the receptor.

Another compound that I have been following with data at Molecular Targets is ABT-199/GDC-199.

You’ll find me in the poster halls every afternoon, so if you are going to be in Boston for Molecular Targets, I look forward to seeing you there!

Photoimmunotherapy (PIT) that uses a near-infrared (NIR) dye conjugated to monoclonal antibodies (mABs) that target epidermal growth factor receptors (EGFR) is a new type of molecular-targeted cancer therapy that appears to offer considerable promise.

Research by Makoto Mitusnaga and colleagues from the Molecular Imaging Program at the National Cancer Institute (NCI) was published recently in Nature Medicine. This paper is well worth reading if you have an interest in this area.

The NCI researchers developed a:

“mAb-based photosensitizer that is activated by NIR light for targeted PIT only when bound to the target molecule on the cancer cellular membrane.”

I think this is exciting research because unlike conventional photodynamic therapy that also damages normal tissue, photoimmunotherapy kills only antibody-bound cancer cells with no normal tissue damage:

“Further, because this agent also emits a diagnostic fluorescence, it can be used to direct the application of light to minimize exposure to nonrelevant tissues and to noninvasively monitor any therapeutic effects of excitation light.”

You can read more in the Nature Medicine paper about this exciting research that may offer an innovative new drug delivery mechanism for targeted cancer therapies.

ResearchBlogging.orgMitsunaga, M., Ogawa, M., Kosaka, N., Rosenblum, L., Choyke, P., & Kobayashi, H. (2011). Cancer cell–selective in vivo near infrared photoimmunotherapy targeting specific membrane molecules Nature Medicine DOI: 10.1038/nm.2554

San Francisco – “Translational research is the key to successful drug development” according to William N. Hait MD, PhD, global therapeutic area head of oncology, Johnson & Johnson.

Hait presented a plenary session on “overcoming barriers to new drug development” at the recent AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics International Conference in San Francisco.

How do we define translational research?

The definition Hait most likes is from Duke Ellington: “if it sounds good, it is good

The challenge of drug development is that with rare exceptions the process is slow, inefficient and expensive.

Hait outlined several challenges to translational research, including:

  • Complexity – imagine blocking the traffic in mid-town manhattan. If you blocked one cross-town route, traffic would slow and then find another route.

This in my opinion is a good visual metaphor for the cross-talk that occurs in cancer. Block one target, and the cancer finds another route.  This highlights the need for combination therapy.

rational combinations of targeted agents may require studying two or more unapproved agents” said Hait.

Novel-novel combinations are something that many companies are nervous about, but if there is a solid scientific rationale then this is something I think we will see more companies doing.

For further insight into how academia is facilitating this type of combination trials, I recommend Sally Church’s interview on Pharma Strategy Blog with Gordon Mills at ECCO/ESMO in Stockholm.

  • Inaccuracy of preclinical models – our models don’t always predict preclinically what activity a drug will have in the clinic.
  • Efficacy of Clinical Trial Recruitment  – need to have alignment of incentives. 20% of US patients are eligible for clinical trials, but only 3% participate.
  • Developing Biomarkers.  Difficult to obtain serial biopsies for oncology biomarker analysis.  Circulating tumor cells may be future, but current instruments can only capture and enumerate and offer limited characterization. According to Hait, the next–generation platform will be exciting.  It will allow third parties to offer additional functionality that can be integrated with the platform.
  • Drug resistance – a nemesis that just doesn’t want to go away.
  • Overcoming the Regulatory Environment – challenges include: scientific complexity, endpoint consistency, global harmonization, companion diagnostic tests, proper comparators, equipoise.

In spite of this complexity, Hait noted the FDA approved 34 new drugs in 2011. Several cancer drugs had a short time from submission to approval and met their PDUFA target date.  “These are incredible accomplishments,” he said.

  • Market Access – Hait asked the audience: “Would you buy a Porsche 911 that only works for 20% of the people, but we don’t know if you are one of the 20%?” Healthcare authorities need to decide cost/benefit of drugs, and regulatory approval does not automatically mean a new product will be reimbursed. There may be need for future trials with health comparators, or innovative agreements where the healthcare authority only pays for those patients who respond.
  • Workforce – academic physicians may end up being segmented into three groups: master clinicians, clinical investigators, physician-scientists. This may provide better career development than the current system.

Hait offered a few suggestions for improvement:

  • Move to phenotypic screening rather than target-based screening. In vivo shRNA screening was discussed.
  • Disease based drug discovery teams – the hope is that in-depth focused teams will predict better results.
  • More intense academic-industry collaboration with a focus on complementary expertise.

The limitation of this plenary presentation was that it only offered the perspective of one senior industry professional. I would have welcomed a balance of views on the barriers to new cancer drug development, and more focused take-home solutions.

If you want to hear more on this topic, AACR have a free podcast that you can download of an interview they did with Dr Hait at the Molecular Targets meeting.

1 Comment
error: Content is protected !!