Currently, Merrimack is conducting a phase 2 trial evaluating MM-141 (monoclonal antibody that acts as a tetravalent inhibitor of PI3K/AKT/mTOR) in patients with metastatic pancreatic cancer. This study is testing MM-141 in combination with nab-paclitaxel (Abraxane-albumin-bound) and gemcitabine in the front-line setting.
Overcoming cancer's defense
What often makes cancer cells tough to treat is their ability to fool the immune system into thinking that they're harmless. They do that by sending a signal to a receptor on a patient's immune system's T-cells, which are known as PD-1, that effectively render the T-cell inactive. Opdivo overcomes this defense by blocking the PD-1 receptor from being able to receive the cancer cell's message to turn itself off, thereby allowing T-cells to continue identifying and destroying cancer cells.
Last year, Bristol-Myers Squibb and Celgene announced that they'll study a one-two punch combination approach in pancreatic cancer that combines Opdivo with Celgene's Abraxane, a chemotherapy drug. Abraxane (paclitaxel protein-bound particles for injectable suspension, albumin-bound) to treat patients with late-stage (metastatic) pancreatic cancer.
Why not Opdivo + MM-398 (ONIVYDE)
Hopefully the collaboration is still ongoing and Merrimack will supply Allergan/Pfizer with a generic doxorubicin HCl liposome injection.
MERRIMACK PHARMACEUTICALS FORM 10-Q (Quarterly Report)
Filed 11/09/15 for the Period Ending 09/30/15
"In November 2013, we entered into a development, license and supply agreement with Watson Laboratories, Inc., or Actavis, which we refer to as the Actavis agreement, pursuant to which we will develop, manufacture and exclusively supply the bulk form of doxorubicin HCl liposome injection, or the initial product, to Actavis. Under the Actavis agreement, Actavis is responsible for all costs related to finished product processing and global commercialization. *****Pursuant to the Actavis agreement, we have ALSO agreed to develop additional products for Actavis in the future, the identities of which will be mutually agreed upon.*****"
"Therefore, we have recorded $3.9 million and $3.8 million of total billed and billable milestones and development expenses related to the Actavis agreement as deferred revenue as of September 30, 2015 and December 31, 2014, respectively. We expect to recognize this revenue over the ten year period that begins after Actavis’ first sale of applicable product under the Actavis agreement."
Allergan has the following doxorubicin products currently on its website:
DOXORUBICIN HCL 10MG/5ML INJ 5ML VL
DOXORUBICIN HCL 200MG/100ML INJ 100ML VL
DOXORUBICIN HCL 20MG/10ML INJ 10ML VL
DOXORUBICIN HCL 50MG/25ML INJ 25ML VL
Merrimack shares double-digit profits with Allergan on future global sales of any commercialized products derived from the collaboration. Merrimack will be responsible for manufacturing bulk product at its Cambridge, Mass. nanoliposomal manufacturing facility.
In November 2013, we entered into an agreement with Actavis (now Allergan) where Merrimack will utilize its proprietary nanoliposomal technology platform to develop and manufacture various pharmaceutical products for Actavis to commercialize around the world. We will produce bulk drug product at our Cambridge, MA nanoliposomal manufacturing facility.
Ok, I see what you mean.
Great find! Thanks for posting!
Merrimack, as a company, is listed under the AVARX category of "Oncology - Solid Tumors" on the AVARX website, but MM-121 is not listed among their one-hundred and nineteen (119) "Oncology - Solid Tumors" opportunities or any other opportunities.
To test the AVARX system, I typed in the opportunity "EGFL7 Peptides" offered by Western in the search box, and it comes up, no problem.
So, why is MM-121 nor MM-398 not showing up through the search box?
Only when I Google "AVARX MM-398 MM-121" do I find an AVARX link to these opportunities which shows MM-398 as sold and MM-121 "Last Updated on March 7, 2015" and MM-121 search by itself shows an update of Aug 24, 2015.
My guess is there is a bug in the AVARX system that Merrimack and AVARX need to be made aware of so that the candidates show up when searched for by name or company, or Merrimack pulled their ad with AVARX for some "reason" and we are seeing uncleared residual of the old listings on the AVARX site.
I think the latter may be true because if you type in Merrimack on the AVARX site and hit listings, it show "Total listings: 0" Whereas "University of Western Ontario" lead to the opportunity above.
So, something happened since Aug 24, 2015 which is a recent event????
Multistem for MI is total BS.
Go to: circres ahajournals org content 110 2 304 full pdf html
Look at Figures 3 and 4.
There is no trend with Multistem doses. Only a striking bump for the 50 million that is significant in Figures 3A and 4B but with major inconsistencies for the 20 and 100 million cell doses. This data is not convincing at all.
Autologous heart stem cells from the unaffected region of the heart and placenta amniotic membrane offer much better options that Multistem. MI is NOT Multistem's forte.
The spleen is a "good thing" for heart attacks, per Harvard:
"In a ground-breaking study published in Science 2009, researchers at the Center for Systems Biology (CSB) showed that the spleen, an organ previously regarded as somewhat redundant, in fact plays a key role in the healing response following a heart attack. As it happens, the spleen functions as a reservoir for specific immune cells, known as monocytes. Up until this discovery, the bone marrow was believed to be the sole source of these cells, not only producing them, but also releasing them into the blood stream to circulate the body and respond to signs of injury or inflammation. The investigation published in Science, however, was the first to show that following injury to the heart, it is the spleen-derived monocytes, rather than those in circulation, that play the major role in repair."
I agree, Multistem is perfect for ARDS as well as sepsis and late stage pulmonary TB. Gil should pursue all foreign and domestic funding opportunities for these indications.
As for acute myocardial infarction (AMI), Athersys' Multistem will fail miserably for this targeted indication, which is much better addressed by placenta amniotic membrane.
The indications I see as viable for Multistem are: stroke, ARDS, sepsis, TB, and other injuries causing a
peripheral immune response that mediates, by the spleen, inflammation that enhances neurodegeneration.
Acute spinal cord Injury, within 24 hours, fits this criteria.
Multistem for AMI is a horrible idea and the last on my list of likely success and doomed to complete failure. Horrible idea. Horrible!
Pfizer designed the MultiStem(R) Cell Therapy for Ulcerative Colitis to fail because they only used a single dose on ten year old chronic patients knowing Osiris' Prochymal required multiple doses to see a response.
Chugai is an oncology company with no commitment to stroke. They gambled $10 million on a one-off chance in the phase 2. They lost because Gil changed the acceptance criteria to include patients 48 hours post-stroke from 36 hours. This is too long, and the trial failed. Chugai has no long-term sticktoitiveness when it comes to stroke.
Gil has a chance to break new ground with Multistem for TB rescue. The lung, combined with the spleen, is the immunomodulatory sweet spot for Multistem. Again, the emerging theme here is that Multistem benefits ARDS (Acute Respiratory Distress Syndrome), sepsis (The most common cause of ARDS -Mayo Clinic), and TB.
There are many avenues to initiate Multistem for late stage TB rescue, starting with the FDA which has already established orphan and neglected diseases approval routes.
Investigator sponsored trials in other countries would be a cost-free way to showcase Multistem for TB. Why not?
The emerging theme here is that Multistem benefits ARDS (Acute Respiratory Distress Syndrome), sepsis (The most common cause of ARDS -Mayo Clinic), and TB (Arch Immunol Ther Exp (Warsz). 2015 Dec;63(6):427-33, The Lancet Respiratory Medicine Volume 2, No. 2, p108–122, February 2014 ).
The question is:
There are way to make this happen free of cost.
"This splenic response to ischemic injury is similar in all other tissues and organ systems indicating that this is a general physiologic response to ischemia. Thus, our opinion is supported by these numerous studies that show the efficacy of the removal of the spleen in reducing infarct volume after middle cerebral artery occlusion (MCAO)."
Journal of Cerebral Blood Flow & Metabolism (2015) 35, 186–187
Did you go to the clinical trial design they used for the MSC TB trial? Their trial actually produced interesting results, albeit phase 1. TB is not stroke.
Because he was certainly MORE right BEFORE changing the time to a maximum of 48 hours...which failed the phase 2 stroke trial out.
0 hours is obviously too early.
The spleen starts to dump pro-inflammatory cells at ~6 hours.
Cerebral ischaemia induces release from bone marrow at ~4 hours. Microglia contribution to inflammation is even sooner.
This all lasts ~22 hours.
Multistem for stroke should be given no later than 24 hours for best response based on these facts. I am not sure of the earliest time, maybe 10-12 hours?
The limited data is leading Gil toward 36 hours is a bit on the long side and if he is wrong could sink our ship. Better hope he is right.
FDA's Efforts on Rare and Neglected Diseases
Jesse L. Goodman, M.D., M.P.H.
Chief Scientist and Deputy Commissioner for Science and Public Health
Food and Drug Administration
Department of Health and Human Services
the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies
Committee on Appropriations
United States Senate
June 23, 2010
Good afternoon Chairman Kohl and Members of the Subcommittee. I am Dr. Jesse L. Goodman, Chief Scientist and Deputy Commissioner for Science and Public Health at the Food and Drug Administration (FDA). I appreciate the opportunity to be here today to describe the role of FDA in encouraging and speeding the development of drugs, vaccines, and diagnostic tests for rare and neglected diseases.
There are more than 6,000 rare diseases, defined by the Orphan Drug Act as a disease affecting fewer than 200,000 people in the U.S., and numerous neglected diseases that predominantly affect impoverished or disenfranchised populations of the developing world. Around the world, more than one billion people are affected by at least one neglected disease, such as tuberculosis (TB), malaria, hookworm infection, and leprosy.
17 November 2015
GENEVA - The Board of the Global Fund to Fight AIDS, Tuberculosis and Malaria approved a new framework for its 2017-2022 strategy to maximize impact, strengthen systems for health, promote and protect human rights and gender equality, and mobilize additional resources.
At a two-day Board meeting, partners agreed to prioritize efforts that reach more people and achieve greater impact through innovative approaches that meet diverse country needs. The Global Fund invests nearly US$4 billion each year in programs in communities and countries all over the world to accelerate the end of HIV, TB and malaria as epidemics.