OX40 Protein Source: Emw http://bit.ly/1Fww0kP

Haberman Associates has a new website, with the same URL as previously but with many improvements. This article is the first Biopharmconsortium Blog post to be posted after the new website has gone online. Please explore the new site, and send any comments on the site to us.

In addition to announcing our new website, this article is designed to outline several new areas of cancer immunotherapy R&D.

Research and development of novel checkpoint inhibitors for cancer immunotherapy

Our September 2014 book-length Insight Pharma Report, “Cancer Immunotherapy: immune checkpoint inhibitors, cancer vaccines, and adoptive T-cell therapies” focused on agents that had reached the clinic. In the case of checkpoint inhibitors, the report did not cover the universe of immune checkpoints, but only those that have been addressed with late-stage agents, some of which had entered—or were about to enter—the market. However, as we stated in the report, researchers expect new experimental products to emerge from immune checkpoint research in the next 5-10 years.

In the report, we mentioned research on agents to target the lymphocyte-activation gene 3 (LAG-3, CD223) pathway. In a published study in mice, Bristol-Myers Squibb (BMS) researchers and their academic collaborators obtained evidence that dual treatment with an anti-PD-1 (such as BMS’ nivolumab) and an anti-LAG-3 monoclonal antibody (MAb) cured most mice of established tumors that were largely resistant to single antibody treatment. They concluded that dual blockade of PD-1 and LAG-3 might constitute a viable strategy for cancer immunotherapy, which might be superior to blocking PD-1 alone.

At the time of our report’s publication, BMS had initiated two Phase 1 safety studies with an investigational anti-LAG-3 MAb. These are a study of anti-LAG-3 with and without anti-PD-1 in treatment of solid tumors (clinical trial number NCT01968109), and a study of anti-LAG-3 in relapsed or refractory chronic lymphocytic leukemia (CLL), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) (clinical trial number NCT02061761). Both of these studies are still ongoing and recruiting patients.

Another checkpoint inhibitor target that is begin investigated (in preclinical studies) for potential use in cancer immunotherapy is TIM-3 (T-cell immunoglobulin domain and mucin domain 3). TIM-3 is is co-expressed on PD-1+ CD8 T cells in mouse models with solid tumors or hematologic malignancies. In a preclinical mouse melanoma model, combined blockade of TIM-3 and PD-1, or TIM-3 and CTLA4, was more effective in prolonging survival than blocking either protein alone. Moreover, the combination of anti-CTLA4, anti-TIM-3 and anti-LAG-3 produced further suppression of growth of the melanoma tumor. These data suggest that blockade of multiple inhibitory receptors—including TIM-3 and LAG-3—results in synergistic antitumor activity.

Research and development of agonist antibodies for use in cancer immunotherapy

Another approach to antibody-based cancer immunotherapy—in addition to targeting checkpoint inhibitors—is development of agonist antibodies. This is the subject of an upcoming conference in Boston—sponsored by Cambridge Healthtech Institute (CHI), on May 7-8, 2015. This conference is part of CHI’s annual PEGS Boston (Essential Protein Engineering Summit). Agonist antibodies target certain cell surface proteins on T cells, resulting in stimulation of the activity of the T cells. This contrasts with checkpoint inhibitors, which are designed to overcome blockages to T cell activity mediated by immune checkpoints.

Among the targets for agonist antibodies are two members of the tumor necrosis receptor (TNFR) superfamily—CD27 and OX40.

Celldex Therapeutics’ fully-human monoclonal antibody (MAb) agent varlilumab (CDX-1127) targets CD27. As discussed in our cancer immunotherapy report, activation of naïve T-cells requires both T-cell receptor (TCR) signaling and costimulation by a “second signal”. In our report, we used the example of CD28 (present on the surface of T cells) interacting with B7 [present of the surface of an antigen-presenting cell (APC) such as a dendritic cell] to deliver a “second signal”. CD27 is a member of the CD28 superfamily, and it interacts with CD70 to deliver a “second signal”. Varlilumab can substitute for CD70, and deliver a costimulatory signal to T cells whose TCRs are engaged. This can change a weak immune response into a strong, prolonged response. In preclinical models, immunostimuation by varlilumab has been shown to mediate antitumor effects.

In addition to the immunostimulatory activity of varlilumab, this agent may also exert direct therapeutic effects against tumors that express CD27 at high levels, such as human B and T cell lymphomas. Varlilumab has shown potent anti-tumor activity against these lymphomas in preclinical models. In these models, varlilumab may exert its therapeutic activity both via “second-signal” immune activation, and via direct antitumor activity against CD27-bearing lymphoma cells.

Varlilumab is now in ongoing Phase 1 clinical trials against solid and hematological tumors (clinical trial number NCT01460134), and in ongoing Phase 1 and Phase 2 trials in combination with the anti-PD-1 MAb agent nivolumab (BMS’ Opdivo) against advanced refractory solid tumors (clinical trial number NCT02335918). Reports of interim data from clinical trials of varlilumab at scientific meetings in 2013 and in 2014 indicate that this agent was very well tolerated and demonstrated biological activity and signs of clinical activity against advanced, treatment-refractory lymphoid malignancies and metastatic melanoma and renal cell carcinoma.

On March 17, 2015 Celldex announced that it had entered into an agreement with Roche to evaluate the safety, tolerability and preliminary efficacy of varlilumab in combination with Genentech/Roche’s investigational anti-PDL1 agent MPDL3280A in a Phase 1/2 study in renal cell carcinoma. This is based on preclinical studies that suggest that the combination of these two agents may be synergistic, and enhance anti-tumor immune response as compared to either agent alone. In Celldex’s Phase 1 study of varlilumab in multiple solid tumors, promising signs of clinical activity had been seen in patients with refractory renal cell carcinoma. This included a durable partial response (11.0+ months) with decreases in tumor volume over time, and 4 patients with stable disease over periods ranging from 5.3 to 30.7+ months.

Another target for agonist MAbs in immuno-oncology is OX40. MedImmune (the global biologics R&D arm of AstraZeneca) is testing the OX40 agonist MAb MEDI6383 in an ongoing Phase 1 clinical trial (clinical trial number NCT02221960) against recurrent or metastatic solid tumors. MedImmune’s OX40 program is based on technology developed by AgonOx (Portland, OR). The two companies entered into an exclusive global partnership to develop OX40 agonists in 2011.

OX40 is a costimulatory receptor that can potentiate TCR signaling in T cells, leading to the activation of these cells by antigens recognized by their TCRs. Engagement of OX40 by its natural ligands on dendritic cells, or by anti-OX40 antibodies initiates a signal transduction cascade that enhances T cell survival, proliferation, and cytokine production, and can augment immune responses to tumors. Preclinical studies have shown that OX40 agonist antibodies increase antitumor immunity and improve tumor-free survival. A Phase 1 clinical study of an mouse anti-OX40 agonist MAb in patients with advanced cancer was carried out by researchers at the Providence Portland Medical Center in Portland, OR. (AgonOx is a spin-off of the Providence Portland Medical Center.) The study (clinical trial number NCT01644968), whose results were published in 2013, found that treatment with one course of the anti-OX40 MAb induced regression of at least one tumor metastasis in 12 of 30 patients, and exhibited an acceptable toxicity profile. Treatment with the agent also increased the antitumor reactivity of T and B cells in patients with melanoma.

In the upcoming CHI agonist antibody conference, Scott A. Hammond, Ph.D., Principal Scientist, Oncology Research at MedImmune will discuss the preclinical characterization of MedImmune’s OX40 agonists now in clinical trials.

Conclusions

The studies on novel immune checkpoint inhibitors and agonist antibodies illustrate that researchers are continuing to advance the frontiers of immuno-oncology beyond the late-stage MAb agents described in our report. Moreover, many of these studies involve clinical trials of combination therapies of the novel agents with other therapeutics discussed extensively in our report, including the CTLA-4 inhibitor ipilimumab (Medarex/BMS’s Yervoy), the PD-1 inhibitors nivolumab (BMS’ Opdivo) and pembrolizumab (Merck’s Keytruda), and the PD-L1 inhibitor MPDL3280A (Genentech/Roche). This is consistent with the idea that “the future of cancer immunotherapy is combination therapy”. In the survey that Insight Pharma Reports conducted in conjunction with our report, 80% of respondents agreed with this statement.

As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to your company, please contact us by phone or e-mail. We also welcome your comments on this or any other article on this blog.

The post Our new website, and continuing R&D on antibody drugs for cancer immunotherapy appeared first on Haberman Associates.

Agios Kirykos, Ikaria, Greece. Source: http://commons.wikimedia.org/wiki/File:Agios_Kirikos,_Ikaria.jpg

Because of being very busy with other projects, we have not posted an article on this blog since April 10, 2014. However, the Biopharmconsortium Blog is still here. More importantly, Haberman Associates biotech/pharma consulting is still here, and we’re still accepting new clients.

Thanks to the many readers who have continued to follow our website and blog during our blogging hiatus, and who have linked to our blog on Twitter and on other social media.

During the hiatus, several of the companies that we have been following on our blog have been progressing. Over the next several months, we shall be blogging about some of these companies, as well as about other notable industry events that have occurred in recent weeks and that will occur during the remainder of 2014.

The first company that we are writing about is cancer metabolism specialist Agios Pharmaceuticals (Cambridge, MA). Our most recent three articles about Agios on this blog are:

• https://biopharmconsortium.com/blog/2012/12/28/haberman-associates-in-chemical-engineering-news-cen-article-on-agios-pharmaceuticals/
• https://biopharmconsortium.com/blog/2013/06/17/agios-pharmaceuticals-files-for-an-ipo/
• https://biopharmconsortium.com/agios-pharma-becomes-a-clinical-stage-company

In our September 23, 2013 article, we noted that Agios had initiated its first clinical study—a Phase 1 clinical trial of AG-221 in patients with advanced hematologic malignancies bearing an isocitrate dehydrogenase 2 (IDH2) mutation. AG-221 is a first-in-class, orally available, selective, potent inhibitor of the mutated IDH2 protein. It is thus a targeted (and personalized) therapy for patients with cancers with an IDH2 mutation.

On June 14, 2014, Agios reported on new clinical data in its ongoing Phase 1 trial of AG-221, which was presented at the 19th Congress of the European Hematology Association (EHA) in Milan, Italy by Stéphane de Botton, M.D. (Institut de Cancérologie Gustave Roussy, Villejuif, France).

The presentation reported on the results of AG-221 treatment of 35 patients with IDH2 mutation positive hematologic malignancies. The researchers observed objective responses in 14 out of 25 evaluable patients, and stable disease in an additional 5 patients. Six patients experienced complete remissions which lasted from one to four months, and are still ongoing. AG-221 has shown favorable pharmacokinetics at all doses tested, with large reductions in serum levels of the oncometabolite 2-hydroxyglutarate (2HG). AG-221 was also well tolerated.

The new data confirms and builds upon previously results. The favorable safety and efficacy data supports Agios’ plan to initiate four expansion cohorts in the second half of 2014. Agios also expects to submit additional data from the ongoing Phase 1 trial for presentation at a later scientific meeting in 2014.

Meanwhile, as announced on June 13, 2014, Agios’ partner Celgene exercised its option to an exclusive worldwide license for AG-221. It exercised this option early, based on the Phase 1 data generated so far.

On June 16, 2014, Agios announced that the FDA granted orphan drug designation for AG-221 for treatment of patients with acute myelogenous leukemia (AML). On August 13, 2014, the FDA also granted Fast Track designation to AG-221 for the treatment of patients with AML that carry an IDH2 mutation.

Thus development of Agios’ lead compound, AG-221, continues to progress. Several other Agios R&D programs are also progressing, as detailed in the company’s report for the second quarter of 2014.

As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to your company, please contact us by phone or e-mail. We also welcome your comments on this or any other article on this blog.

The post Agios Pharmaceuticals continues to progress appeared first on Haberman Associates.

Happy New Year! Source: Roblespepe. http://bit.ly/1cpkyHX

As it does every year, Science published its “Breakthrough of the Year” for 2013 in the 20 December 2013 issue of the journal.

Science chose cancer immunotherapy as its Breakthrough of the Year 2013.

In its 20 December 2013 issue, Science published an editorial by its Editor-in-Chief, Marcia McNutt, Ph.D., entitled “Cancer Immunotherapy”. The same issue has a news article  by staff writer Jennifer Couzin-Frankel, also entitled “Cancer Immunotherapy”.

As usual, the 20 December 2013 issue of Science contains a Breakthrough of the Year 2013 news section, which in addition to the Breakthrough of the Year itself, also contains articles about several interesting runners-up, ranging from genetic microsurgery using CRISPR (clustered regularly interspaced short palindromic repeat) technology to mini-organs to human cloning to vaccine design.

In the Science editorial and news article, the authors focus on the development and initial successes of two types of immunotherapy:

• Monoclonal antibody (MAb) drugs that target T-cell regulatory molecules, including the approved CTLA4-targeting MAb ipilimumab (Bristol-Myers Squibb’s Yervoy), and the clinical-stage anti-PD-1 agents nivolumab (Bristol-Myers Squibb) and lambrolizumab (Merck).
• Therapy with genetically engineered autologous T cells, known as chimeric antigen receptor (CAR) therapy, such as that being developed by a collaboration between the University of Pennsylvania and Novartis.

The rationale for Science’s selection of cancer immunotherapy as the breakthrough of the year is that after a decades-long process of basic biological research on T cells, immunotherapy products have emerged and–as of this year–have achieved impressive results in clinical trials. And–as pointed out by Dr. McNutt–immunotherapy would constitute a new, fourth modality for cancer treatment, together with the traditional surgery, radiation, and chemotherapy.

However, as pointed out by Dr. McNutt and Ms. Couzin-Frankel, these are still early days for cancer immunotherapy. Key needs include the discovery of biomarkers that can help predict who can benefit from a particular immunotherapy, development of combination therapies that are more potent than single-agent therapies, and that might help more patients, and means for mitigating adverse effects.

Moreover, it will take some time to determine how durable any remissions are, especially whether anti-PD1 agents give durable long-term survival. Finally, although several MAb-based immunotherapies are either approved (in the case of  ipilimumab) or well along in clinical trials, CAR T-cell therapies and other adoptive immunotherapies remain experimental.

In addition to the special Science “Breakthrough 2013” section, Nature published a Supplement on cancer immunotherapy in its 19/26 December 2013 issue. This further highlights the growing importance of this field.

Cancer immunotherapy on the Biopharmconsortium Blog

Readers of our Biopharmconsortium Blog are no strangers to recent breakthroughs in cancer immunotherapy. In the case of MAb-based immunotherapies, we have published two summary articles, one in 2012 and the other in 2013. These articles noted that cancer immunotherapy was the “star” of the American Society of Clinical Oncology (ASCO) annual meeting in both years.

Our blog also contains articles about CAR therapy, as being developed by the University of Pennsylvania and Novartis and by bluebird bio and Celgene. Moreover, the Biopharmconsortium Blog contains articles on other types of cancer immunotherapies not covered by the Science articles, such as cancer vaccines.

We look forward to further progress in the field of cancer immunotherapy, and to the improved treatments and even cures of cancer patients that may be made possible by these developments.

As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to  your company, please contact us by phone or e-mail. We also welcome your comments on this or any other article on this blog.

The post Breakthrough of the year 2013–Cancer Immunotherapy appeared first on Haberman Associates.

Eastern Bluebird

The Biopharmconsortium Blog includes several articles that are–in whole or in part–about adoptive T-cell immunotherapy [or adoptive cell transfer (ACT)] for cancer. In particular, we have produced two blog articles that discuss the Novartis/University of Pennsylvania (Penn) collaboration, which is aimed at finally commercializing adoptive immunotherapy for cancer.

• “Is Novartis Building A Viable Business Model For Adoptive Immunotherapy For Cancer?” (September 28, 2012)
•  “Leukemia–Going For The Cure!” (July 29, 2013 )

The Novartis/Penn collaboration focuses on a particular technology for ACT, known as chimeric antigen receptor (CAR) technology. In this technology, autologous T cells isolated from patient blood are engineered with retroviral vectors carrying a gene for a tumor antigen-specific CAR. The CAR enables the engineered cells to recognize specific surface proteins on tumor cells, and to go on to kill the cells.

Now we find out that at least one more company–one a lot closer to home (at least for us folks in Greater Boston)–is involved in a collaboration to develop and commercialize CAR technology for ACT. This company is bluebird bio (Cambridge, MA). As of June 24, 2012, bluebird successfully completed its initial public offering.

On March 21, 2013, bluebird announced in a press release that it had entered into a multi-year strategic collaboration with Celgene (Summit, NJ) to discover new disease-modifying gene therapies for cancer. The collaboration is to focus on applying bluebird’s gene therapy technology to the design and development of CAR T cells.

According to the news release, the bluebird/Celgene collaboration may lead to the development and commercialization of multiple CAR T-cell products. Celgene has an option to license products that result from the collaboration after the completion of a Phase 1 clinical trial for each product. bluebird bio will be responsible for R&D through Phase 1 clinical trials, and Celgene will be responsible for clinical studies beyond Phase 1 for any product that it licenses, as well as commercialization of any such product.

As also announced in the March 21, 2013 press release, Celgene has entered into a separate strategic collaboration that focuses on CAR T-cell technology with the Center for Cell and Gene Therapy at Baylor College of Medicine, Texas Children’s Hospital and The Methodist Hospital (Houston, TX). The work on CAR T-cell technology in Houston is led by Malcolm Brenner, M.D., Ph.D. (Director, Center for Cell and Gene Therapy Baylor College of Medicine). Dr. Brenner and his colleagues, for example, showed that T cells expressing a CAR specific for the GD2 tumor antigen on neuroblastoma cells produced tumor responses in over half of 19 neuroblastoma patients with refractory or active disease. Three of 11 patients with active disease achieved complete remission.

According to the March 21, 2013 news release, bluebird bio, Celgene and Dr. Brenner’s team will work collaboratively to advance and develop existing and new CAR T-cell products and programs.

Our October 2012 discussion of bluebird bio and adoptive cell transfer in the Biopharmconsortium Blog

On  October 11, 2012, we published an article on this blog entitled “Is Gene Therapy Emerging From Technological Prematurity?” This article included a section on bluebird bio, which represented the very first time we mentioned bluebird on this blog.

In this section–over 5 months before bluebird announced its agreement with Celgene–we discussed the relationship between bluebird’s technology and ACT:

bluebird bio’s platform..represents both a gene therapy technology and an adoptive cellular transfer (ACT) technology. We have discussed ACT technologies (in this case, for immunotherapy for cancer) in a previous article on this blog.  Since some of these technologies involve genetically-engineered autologous T cells, they may also be thought of as representing both ACT and a kind of gene therapy.

We are happy to learn that bluebird also realized (independent from us) the potential utility of their “gene therapy” technology for adoptive immunotherapy/ACT for cancer. We are also happy that bluebird entered into an agreement with Celgene to develop and commercialize such therapies, with the potential to give at least some cancer patients the durable complete responses that they yearn for.

As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or an initial one-to-one consultation on an issue that is key to your company’s success, please contact us by phone or e-mail. We also welcome your comments on this or any other article on this blog.

The post Bluebird Bio, Celgene, and Adoptive Immunotherapy for Cancer appeared first on Haberman Associates.

Haberman Associates now has a new website, which is available at https://biopharmconsortium.com. Our new site has an attractive, up-to-date look and feel, and also contains updated news and other updated content.

We have also fully integrated our Biopharmconsortium Blog into our new site. Our blog resides at https://biopharmconsortium.com/blog. There has been a hiatus in posting on our blog recently, due to finishing construction of our new site. Thus the last article on our blog before completion of the website was posted on April 5, 2013. However, we posted a new article on May 29, 2013, and intend to publish blog articles on a more regular basis.

The integration of the Biopharmconsortium Blog into our website emphasizes that it is the blog for our consulting group, not an independent entity or a  journalistic blog. Despite the diversity of subjects covered by the blog, the focus is on effective drug discovery and development, and on company strategies designed to facilitate effective new product development.

For more information on our consulting group, Haberman Associates, see our brief December 16, 2012 blog article, entitled What Is Haberman Associates? Better yet, you may explore our website for a more complete picture of our consulting group.

We hope that the diverse community of our readers will benefit from the discussions on our blog. We also hope that those of you in life science companies will get a feeling for how we approach issues in drug discovery and development and company strategies.

However, even the best articles or books on how to solve key industry problems will not solve these problems on their own. Companies need to develop company-specific solutions and to implement them. Haberman Associates consulting may enable your company to formulate and implement the solutions you need to improve your productivity.

If you are in  a life sciences firm, and have questions about Haberman Associates, or wish to send us a consulting inquiry or to commission us to write a report for publication, please telephone or e-mail us.

The post Haberman Associates has a new website! appeared first on Haberman Associates.

A few weeks ago, I attended a presentation that was produced by another consulting firm, which we shall call Company X. They began their presentation with a discussion of “what is Company X?” Then they went on the the substance of their presentation.

In the same vein, as the producers of the Biopharmconsortium Blog, this article is entitled “What is Haberman Associates?” After we have posted this article, we also shall go on to our usual subject matter.

Haberman Associates is a Boston-based consulting firm, founded in 1993, that specializes in science and technology strategy for life science companies–principally pharmaceutical, biotechnology, diagnostics, and research products companies, and other companies (e.g., life science publishers, venture capitalists, angel investors, etc.) that serve the industry.

The focus of our company is new product development and commercialization. This includes new products developed via internal R&D and through partnering. In internal R&D, our usual focus is toward the early end of the process–drug discovery and early development.

Clients have used our consulting services to help them:

• discover and develop new drugs, diagnostics, and research products
• improve their drug pipelines
• identify and evaluate potential partners
• develop new applications for their technologies
• penetrate new markets

Haberman Associates is a member the Boston-based Biopharmaceutical Consortium (BPC) and an Affiliate of the North Carolina-based consulting consortium Innovalyst. Our relationship with Innovalyst began after one of our BPC partners moved to North Carolina, and eventually became a Principal of Innovalyst. Between BPC and Innovalyst, we have nearly 90 senior consultants on our team.

We have worked on consulting engagements with both BPC and Innovalyst consultants.  Our relationship with these consortia enables us to take on larger projects, as well as projects requiring multiple types of expertise.

One of my Innovalyst colleagues referred to the Haberman Associates/Innovalyst combination as a “virtual drug discovery and development organization”. Another way to look at the Haberman Associates/Innovalyst combination is as having to power of a single office of a large consulting firm, but one dedicated to helping pharmaceutical and biotechnology clients to increase their effectiveness in the difficult areas of drug discovery and development.

In one case last year, a prospective client asked me whether Haberman Associates could take on a consulting engagement involving GMP services. I know little about that subject, other than where it fits into the process of developing a drug. I also know people who work in that area. So I handed the engagement over to another project leader in Innovalyst. He formed a team that included himself, several domain experts (one of whom knows the Chinese GMP services market), and me.  Although I knew little about GMP services, I used my research and interviewing skills, and made a material contribution to the project. Our team delivered a result that exceeded client expectations.

We always aim to exceed client expectations, whatever the project.

In addition to consulting, Haberman Associates has produced numerous publications–ranging from articles to book-length reports–which have been published by leading life science industry publishers. A list of recent publications is now available on my public LinkedIn profile.

As for the Biopharmconsortium Blog, it is the blog for our consulting group, not a journalistic blog. Despite the diversity of subjects covered by the blog, the focus is on effective drug discovery and development, and on company strategies designed to facilitate effective new product development. We have more good content available than we can possibly blog about, and do not accept requests to blog about content that is irrelevant to our focus.

We hope that the diverse community of our readers will benefit from the discussions on our blog. We also hope that potential clients in the life science industry will get a feeling for how we approach issues in drug discovery and development and company strategies.

However, even the best articles or books on how to solve key industry problems (such as clinical attrition) will not solve these problems on their own. Companies need to develop company-specific solutions and to implement them. For various reasons, they often are unable to do this without outside consulting help. Haberman Associates consulting may enable your company to formulate and implement the solutions you need to improve your productivity.

[Innovalyst ceased to be active as an organization as of February 2013. However, we remain in contact with several Innovalyst Affiliates and Managing Partners, who are available for collaboration with Haberman Associates.]

If you are in  a life sciences firm, and have questions about Haberman Associates, or wish to send us a consulting inquiry or to commission us to write a report for publication, please telephone or e-mail us.

The post What is Haberman Associates? appeared first on Haberman Associates.

As you all may have noticed, we have not had a post on the Biopharmconsortium Blog during the entire month of February, 2012.

This unintended hiatus happened because of the need to finish up other work.

We’re almost finished with these projects, and have several ideas for blog articles (including some articles that we had already started) in the hopper. So the Biopharmconsortium Blog hiatus will end soon.

Thank you very much for your patience, and for your continuing interest in our blog.

The post The Biopharmconsortium Blog hiatus to end soon! appeared first on Haberman Associates.

Happy New Year! http://bit.ly/tKUKIR

We commend for your New Year’s reading the review article entitled “Cancer immunotherapy comes of age” in the 22 December 2011 issue of Nature. It was written by Drs. Ira Mellman (Genentech),  George Coukos (University of Pennsylvania School of Medicine), and Glenn Dranoff (Department of Medical Oncology and Cancer Vaccine Center, Dana-Farber Cancer Center/Brigham and Women’s Hospital and Harvard Medical School, Boston, MA).

As you may recall, Genentech’s Dr. Mellman was mentioned in our November 25, 2011 blog article on Dr. Ralph Steinman. Dr. Mellman was a former member of Dr. Steinman’s lab, and he was one of the researchers who helped plan the strategy for the immunotherapy-based treatment of Dr. Steinman’s own pancreatic cancer.

The review by Dr. Mellman and his colleagues is truly comprehensive. It covers research and events in drug development in cancer immunotherapy that we also discussed in the following 2011 blog articles:

• March 30, 2011: FDA approves ipilimumab (Medarex/Bristol-Myers Squibb’s Yervoy) for treatment of metastatic melanoma.

• April 27, 2011: Adoptive immunotherapy for metastatic melanoma? 

• November 25, 2011: Ralph Steinman, dendritic cell vaccines, and clinical trials.

• December 26, 2011: The 2011 Nobel Prize in Physiology or Medicine–Innate and Adaptive Immunity.

The Nature review ties all these subjects and events together, and gives additional in-depth information on each of them. For example, in discussing adoptive immunotherapy for cancer with tumor infiltrating lymphocytes (TILs), the review presents new studies on the use of T-cell engineering and bispecific antibodies. Such methods may enable researchers and clinicians to get beyond the need for resectable tumors harboring reactive T cells, or even allow them to stimulate TILs in situ, thus avoiding the need to isolate and culture autologous T cells altogether.

Both the new Nature review and the discussions on our blog show that 2011 was a big year for cancer immunotherapy. The past year was proceeded by the 2010 approval of the first ever cancer vaccine, sipuleucel-T (Dendreon’s Provenge) for prostate cancer. 2011 saw the approval of ipilimumab (Medarex/Bristol-Myers Squibb’s Yervoy), and the awarding of a Nobel Prize for discoveries with profound implications for the development of cancer immunotherapies.

The importance for cancer immunotherapy of the discoveries represented by this Nobel Prize was vividly illustrated by the survival of Ralph Steinman an almost incredible four-and-a-half years after his being diagnosed with pancreatic cancer, while receiving a series of immunotherapy treatments along with conventional chemotherapy. (Although there is no way to know whether any of the treatments was responsible for Dr. Steinman’s unexpectedly long survival, participating researchers agree that this one-patient experimental treatment moved the cancer immunotherapy field forward.)

The Nature review concludes that despite the long history of cancer immunotherapy, these are early days for research and clinical practice in the field. (This is typical for a premature technology! Nevertheless, the review concludes, cancer immunotherapy has come of age.

The review goes on to suggest that cancer immuntherapies might be used in combination with the new targeted therapies, such as vemurafenib (Plexxikon/Roche’s Zelboraf; PLX4032) and crizotinib (Pfizer’s Xalkori), which were approved in 2011. These targeted agents can give “significant and sometimes spectacular responses in several indications.” However, even the most dramatic responses are usually followed by drug resistance and relapse. If targeted therapies can be given with the appropriate immunotherapies, it might be possible to achieve long-term, durable responses.

This is the last article on the Biopharmconsortium Blog for 2011. We at Haberman Associates wish you all a very Happy New Year, and look forward to interacting with you in 2012.
__________________________________________

As the producers of this blog, and as consultants to the biotechnology and pharmaceutical industry, Haberman Associates would like to hear from you. If you are in a biotech or pharmaceutical company, and would like a 15-20-minute, no-obligation telephone discussion of issues raised by this or other blog articles, or of other issues that are important to  your company, please click here. We also welcome your comments on this or any other article on this blog.

The post Read the cancer immunotherapy review in the 22 December 2011 issue of Nature! appeared first on Haberman Associates.

I hope that many of you have the special October 2011 issue of The Scientist, celebrating the publication’s 25th anniversary, in your hands. That issue is full of articles by leading researchers, including George Church, E.O. Wilson, Craig Venter, Mary-Claire King, Stephen Friend, and many others.

The Scientist is one of my favorite publications. It helps people in the life sciences industry and academia catch up with new findings that they may have missed in their usual reading, and to learn about areas of the life sciences that are removed from their main professional focus. It also has articles that focus on people in science, thus helping to restore the human element to our field. We also enjoy The Scientist‘s new, improved, and more accessible website.

There are several posts on this blog that are based on articles in The Scientist.

Less than a week after rolling out the celebratory October issue, on Thursday, October 6, The Scientist announced that it was shutting down its operations–another victim of the continuing financial downturn.

However, then came the unexpected reversal. On Friday, October 14, Sciencenow Inc. (the owner of The Scientist) and LabX Media Group announced that they had signed a non-binding Letter of Intent specifying terms for the acquisition of The Scientist by LabX Media Group, and were working to close the deal by the end of October.

On Monday October 17, The Scientist announced, “We’re Back”!  Pending the finalization of the LabX deal the magazine has restarted its operations, both of the print edition and the website. Its editorial staff has remained intact, and is hard at work.

The Scientist says, “We appreciate your patience as we sort out the sale of the magazine and work hard to return to our normal publication schedule. New stories are already appearing on the website, so check there for the latest news and digests from the life sciences….”

“October has been a bit topsy turvy for us, but we can assure you that The Scientist will be back better than ever, and we hope to remain on your desks, in your inboxes, and on your screens for many years to come.”

On October 27, 2011 LabX Media Group announced that it has finalized the acquisition of The Scientist, including print and digital formats, as expected.

Perhaps the bleak economic outlook will not overwhelm us in other areas of our common and our personal life. There is hope.

The post A ray of hope–The Scientist magazine saved from the brink of extinction! appeared first on Haberman Associates.

Then on March 11, 2001, came the 9.0-magnitude Tōhoku earthquake, followed by the devastating tsunami, with the loss of thousands of lives, and extensive damage to the infrastructure of Japan. Particularly troubling is the damage to the Fukushima I nuclear power plant, as well as several other nuclear power plants in Japan, and the uncertainty as to current and future effects of these events on Japan and its people. Also devastating is the economic loss due to the earthquake.

I cannot look at our blog post without thinking about the continuing events in Japan. Our thoughts and prayers are with the Japanese people in their hour of need.

According to a March 14 2011 news release, several employees suffered minor injuries, but all are safe. Two Daiichi Sankyo production facilities in Japan have been partly damaged by the earthquake. The company will assess the situation at these plants–especially with respect to employee safety–as power is restored. Several Daiichi Sankyo sales facilities were also affected by the earthquake, and with employee safety as its first priority, the company will work to restore operations.

The acquisition of Plexxikon by Daiichi Sankyo is on schedule to close at the end of 2011.

Meanwhile, Daiichi Sankyo announced that it would donate 100 million Japanese Yen (JPY) (approximately $1.2 million) to the Japanese Red Cross Society, as well as medical supplies, for relief efforts; it has also implemented a matching gift program for employee donations. Takeda will donate 300 million JPY, as well as medical supplies, and Eisai will donate 200 million JPY and will establish a crisis center in the Tōhoku region. Astellas and Chugai are both donating 100 million JPY.

Non-Japanese Big Pharma and Big Biotech companies–Merck, Abbott, Lilly, GlaxoSmithKline, Johnson & Johnson, and Amgen–are each contributing over $1 million to Japanese aid. Many other corporations outside the pharmaceutical industry have pledged donations for Japanese relief.

The Japanese and American Red Cross, as well as many other secular and religious relief agencies, are assessing the situation in Japan and requesting donations.

Meanwhile, the Japanese people are behaving admirably in this crisis. There has been little or no looting or profiteering, and there is a sense of national cooperation. The resilience of the Japanese people, and their engineering skill and experience in rebuilding from previous disasters, will contribute mightily to Japan’s ability to rebound from this devastating earthquake and tsunami.

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Addendum, March 27, 2011: See the news article in the 22 March 2011 issue of Nature, entitled “The meltdown that wasn’t”.  According to this article, the operators in unit 1 of the Fukushima Daiichi nuclear power station acted competently and courageously in dealing with the effects of the earthquake and tsunami on the reactor on 11 March, 2011. They averted a catastrophic full meltdown of the reactor, and their actions also provided a model for stabilizing the other two reactors at the station.

Radiation exposure due to the Fukushima nuclear accident continues, however, as do the other effects of the earthquake and tsunami on Japan and her people.

For Nature’s full coverage of the continuing story of the Japanese earthquake and nuclear crisis, see http://www.nature.com/news/specials/japanquake/index.html.

The post For the people of Japan appeared first on Haberman Associates.